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Bone & Joint Research
Vol. 12, Issue 10 | Pages 615 - 623
3 Oct 2023
Helwa-Shalom O Saba F Spitzer E Hanhan S Goren K Markowitz SI Shilo D Khaimov N Gellman YN Deutsch D Blumenfeld A Nevo H Haze A

Aims. Cartilage injuries rarely heal spontaneously and often require surgical intervention, leading to the formation of biomechanically inferior fibrous tissue. This study aimed to evaluate the possible effect of amelogenin on the healing process of a large osteochondral injury (OCI) in a rat model. Methods. A reproducible large OCI was created in the right leg femoral trochlea of 93 rats. The OCIs were treated with 0.1, 0.5, 1.0, 2.5, or 5.0 μg/μl recombinant human amelogenin protein (rHAM. +. ) dissolved in propylene glycol alginate (PGA) carrier, or with PGA carrier alone. The degree of healing was evaluated 12 weeks after treatment by morphometric analysis and histological evaluation. Cell recruitment to the site of injury as well as the origin of the migrating cells were assessed four days after treatment with 0.5 μg/μl rHAM. +. using immunohistochemistry and immunofluorescence. Results. A total of 12 weeks after treatment, 0.5 μg/μl rHAM. +. brought about significant repair of the subchondral bone and cartilage. Increased expression of proteoglycan and type II collagen and decreased expression of type I collagen were revealed at the surface of the defect, and an elevated level of type X collagen at the newly developed tide mark region. Conversely, the control group showed osteoarthritic alterations. Recruitment of cells expressing the mesenchymal stem cell (MSC) markers CD105 and STRO-1, from adjacent bone marrow toward the OCI, was noted four days after treatment. Conclusion. We found that 0.5 μg/μl rHAM. +. induced in vivo healing of injured articular cartilage and subchondral bone in a rat model, preventing the destructive post-traumatic osteoarthritic changes seen in control OCIs, through paracrine recruitment of cells a few days after treatment. Cite this article: Bone Joint Res 2023;12(10):615–623


Bone & Joint Research
Vol. 2, Issue 1 | Pages 9 - 17
1 Jan 2013
Xia Y

This review briefly summarises some of the definitive studies of articular cartilage by microscopic MRI (µMRI) that were conducted with the highest spatial resolutions. The article has four major sections. The first section introduces the cartilage tissue, MRI and µMRI, and the concept of image contrast in MRI. The second section describes the characteristic profiles of three relaxation times (T. 1. , T. 2. and T. 1ρ. ) and self-diffusion in healthy articular cartilage. The third section discusses several factors that can influence the visualisation of articular cartilage and the detection of cartilage lesion by MRI and µMRI. These factors include image resolution, image analysis strategies, visualisation of the total tissue, topographical variations of the tissue properties, surface fibril ambiguity, deformation of the articular cartilage, and cartilage lesion. The final section justifies the values of multidisciplinary imaging that correlates MRI with other technical modalities, such as optical imaging. Rather than an exhaustive review to capture all activities in the literature, the studies cited in this review are merely illustrative


Bone & Joint Research
Vol. 9, Issue 9 | Pages 601 - 612
1 Sep 2020
Rajagopal K Ramesh S Walter NM Arora A Katti DS Madhuri V

Aims. Extracellular matrix (ECM) and its architecture have a vital role in articular cartilage (AC) structure and function. We hypothesized that a multi-layered chitosan-gelatin (CG) scaffold that resembles ECM, as well as native collagen architecture of AC, will achieve superior chondrogenesis and AC regeneration. We also compared its in vitro and in vivo outcomes with randomly aligned CG scaffold. Methods. Rabbit bone marrow mesenchymal stem cells (MSCs) were differentiated into the chondrogenic lineage on scaffolds. Quality of in vitro regenerated cartilage was assessed by cell viability, growth, matrix synthesis, and differentiation. Bilateral osteochondral defects were created in 15 four-month-old male New Zealand white rabbits and segregated into three treatment groups with five in each. The groups were: 1) untreated and allogeneic chondrocytes; 2) multi-layered scaffold with and without cells; and 3) randomly aligned scaffold with and without cells. After four months of follow-up, the outcome was assessed using histology and immunostaining. Results. In vitro testing showed that the secreted ECM oriented itself along the fibre in multi-layered scaffolds. Both types of CG scaffolds supported cell viability, growth, and matrix synthesis. In vitro chondrogenesis on scaffold showed an around 400-fold increase in collagen type 2 (COL2A1) expression in both CG scaffolds, but the total glycosaminoglycan (GAG)/DNA deposition was 1.39-fold higher in the multi-layered scaffold than the randomly aligned scaffold. In vivo cartilage formation occurred in both multi-layered and randomly aligned scaffolds treated with and without cells, and was shown to be of hyaline phenotype on immunostaining. The defects treated with multi-layered + cells, however, showed significantly thicker cartilage formation than the randomly aligned scaffold. Conclusion. We demonstrated that MSCs loaded CG scaffold with multi-layered zonal architecture promoted superior hyaline AC regeneration. Cite this article: Bone Joint Res 2020;9(9):601–612


The Bone & Joint Journal
Vol. 103-B, Issue 9 | Pages 1472 - 1478
1 Sep 2021
Shoji T Saka H Inoue T Kato Y Fujiwara Y Yamasaki T Yasunaga Y Adachi N

Aims. Rotational acetabular osteotomy (RAO) has been reported to be effective in improving symptoms and preventing osteoarthritis (OA) progression in patients with mild to severe develomental dysplasia of the hip (DDH). However, some patients develop secondary OA even when the preoperative joint space is normal; determining who will progress to OA is difficult. We evaluated whether the preoperative cartilage condition may predict OA progression following surgery using T2 mapping MRI. Methods. We reviewed 61 hips with early-stage OA in 61 patients who underwent RAO for DDH. They underwent preoperative and five-year postoperative radiological analysis of the hip. Those with a joint space narrowing of more than 1 mm were considered to have 'OA progression'. Preoperative assessment of articular cartilage was also performed using 3T MRI with the T2 mapping technique. The region of interest was defined as the weightbearing portion of the acetabulum and femoral head. Results. There were 16 patients with postoperative OA progression. The T2 values of the centre to the anterolateral region of the acetabulum and femoral head in the OA progression cases were significantly higher than those in patients without OA progression. The preoperative T2 values in those regions were positively correlated with the narrowed joint space width. The receiver operating characteristic analysis revealed that the T2 value of the central portion in the acetabulum provided excellent discrimination, with OA progression patients having an area under the curve of 0.858. Furthermore, logistic regression analysis showed T2 values of the centre to the acetabulum’s anterolateral portion as independent predictors of subsequent OA progression (p < 0.001). Conclusion. This was the first study to evaluate the relationship between intra-articular degeneration using T2 mapping MRI and postoperative OA progression. Our findings suggest that preoperative T2 values of the hip can be better prognostic factors for OA progression than radiological measures following RAO. Cite this article: Bone Joint J 2021;103-B(9):1472–1478


Bone & Joint Research
Vol. 6, Issue 2 | Pages 98 - 107
1 Feb 2017
Kazemi D Shams Asenjan K Dehdilani N Parsa H

Objectives. Mesenchymal stem cells have the ability to differentiate into various cell types, and thus have emerged as promising alternatives to chondrocytes in cell-based cartilage repair methods. The aim of this experimental study was to investigate the effect of bone marrow derived mesenchymal stem cells combined with platelet rich fibrin on osteochondral defect repair and articular cartilage regeneration in a canine model. Methods. Osteochondral defects were created on the medial femoral condyles of 12 adult male mixed breed dogs. They were either treated with stem cells seeded on platelet rich fibrin or left empty. Macroscopic and histological evaluation of the repair tissue was conducted after four, 16 and 24 weeks using the International Cartilage Repair Society macroscopic and the O’Driscoll histological grading systems. Results were reported as mean and standard deviation (. sd. ) and compared at different time points between the two groups using the Mann-Whitney U test, with a value < 0.05 considered statistically significant. Results. Higher cumulative macroscopic and histological scores were observed in stem cell treated defects throughout the study period with significant differences noted at four and 24 weeks (9.25, . sd. 0.5 vs 7.25, . sd. 0.95, and 10, . sd. 0.81 vs 7.5, . sd. 0.57; p < 0.05) and 16 weeks (16.5, . sd. 4.04 vs 11, . sd. 1.15; p < 0.05), respectively. Superior gross and histological characteristics were also observed in stem cell treated defects. Conclusion. The use of autologous culture expanded bone marrow derived mesenchymal stem cells on platelet rich fibrin is a novel method for articular cartilage regeneration. It is postulated that platelet rich fibrin creates a suitable environment for proliferation and differentiation of stem cells by releasing endogenous growth factors resulting in creation of a hyaline-like reparative tissue. Cite this article: D. Kazemi, K. Shams Asenjan, N. Dehdilani, H. Parsa. Canine articular cartilage regeneration using mesenchymal stem cells seeded on platelet rich fibrin: Macroscopic and histological assessments. Bone Joint Res 2017;6:98–107. DOI: 10.1302/2046-3758.62.BJR-2016-0188.R1


The Journal of Bone & Joint Surgery British Volume
Vol. 94-B, Issue 4 | Pages 504 - 509
1 Apr 2012
Bentley G Biant LC Vijayan S Macmull S Skinner JA Carrington RWJ

Autologous chondrocyte implantation (ACI) and mosaicplasty are methods of treating symptomatic articular cartilage defects in the knee. This study represents the first long-term randomised comparison of the two techniques in 100 patients at a minimum follow-up of ten years. The mean age of the patients at the time of surgery was 31.3 years (16 to 49); the mean duration of symptoms pre-operatively was 7.2 years (9 months to 20 years). The lesions were large with the mean size for the ACI group being 440.9 mm. 2 . (100 to 1050) and the mosaicplasty group being 399.6 mm. 2. (100 to 2000). Patients had a mean of 1.5 previous operations (0 to 4) to the articular cartilage defect. Patients were assessed using the modified Cincinnati knee score and the Stanmore-Bentley Functional Rating system. The number of patients whose repair had failed at ten years was ten of 58 (17%) in the ACI group and 23 of 42 (55%) in the mosaicplasty group (p < 0.001). The functional outcome of those patients with a surviving graft was significantly better in patients who underwent ACI compared with mosaicplasty (p = 0.02)


Bone & Joint Research
Vol. 11, Issue 12 | Pages 862 - 872
1 Dec 2022
Wang M Tan G Jiang H Liu A Wu R Li J Sun Z Lv Z Sun W Shi D

Aims. Osteoarthritis (OA) is a common degenerative joint disease worldwide, which is characterized by articular cartilage lesions. With more understanding of the disease, OA is considered to be a disorder of the whole joint. However, molecular communication within and between tissues during the disease process is still unclear. In this study, we used transcriptome data to reveal crosstalk between different tissues in OA. Methods. We used four groups of transcription profiles acquired from the Gene Expression Omnibus database, including articular cartilage, meniscus, synovium, and subchondral bone, to screen differentially expressed genes during OA. Potential crosstalk between tissues was depicted by ligand-receptor pairs. Results. During OA, there were 626, 97, 1,060, and 2,330 differentially expressed genes in articular cartilage, meniscus, synovium, and subchondral bone, respectively. Gene Ontology enrichment revealed that these genes were enriched in extracellular matrix and structure organization, ossification, neutrophil degranulation, and activation at different degrees. Through ligand-receptor pairing and proteome of OA synovial fluid, we predicted ligand-receptor interactions and constructed a crosstalk atlas of the whole joint. Several interactions were reproduced by transwell experiment in chondrocytes and synovial cells, including TNC-NT5E, TNC-SDC4, FN1-ITGA5, and FN1-NT5E. After lipopolysaccharide (LPS) or interleukin (IL)-1β stimulation, the ligand expression of chondrocytes and synovial cells was upregulated, and corresponding receptors of co-culture cells were also upregulated. Conclusion. Each tissue displayed a different expression pattern in transcriptome, demonstrating their specific roles in OA. We highlighted tissue molecular crosstalk through ligand-receptor pairs in OA pathophysiology, and generated a crosstalk atlas. Strategies to interfere with these candidate ligands and receptors may help to discover molecular targets for future OA therapy. Cite this article: Bone Joint Res 2022;11(12):862–872


The Bone & Joint Journal
Vol. 100-B, Issue 3 | Pages 404 - 412
1 Mar 2018
Parker JD Lim KS Kieser DC Woodfield TBF Hooper GJ

Aims. The intra-articular administration of tranexamic acid (TXA) has been shown to be effective in reducing blood loss in unicompartmental knee arthroplasty and anterior cruciate reconstruction. The effects on human articular cartilage, however, remains unknown. Our aim, in this study, was to investigate any detrimental effect of TXA on chondrocytes, and to establish if there was a safe dose for its use in clinical practice. The hypothesis was that TXA would cause a dose-dependent damage to human articular cartilage. . Materials and Methods. The cellular morphology, adhesion, metabolic activity, and viability of human chondrocytes when increasing the concentration (0 mg/ml to 40 mg/ml) and length of exposure to TXA (0 to 12 hours) were analyzed in a 2D model. This was then repeated, excluding cellular adhesion, in a 3D model and confirmed in viable samples of articular cartilage. Results. Increasing concentrations above 20 mg/ml resulted in atypical morphology, reduced cellular adhesion and metabolic activity associated with increased chondrocyte death. However, the cell matrix was not affected by the concentration of TXA or the length of exposure, and offered cellular protection for concentrations below 20 mg/ml. Conclusion. These results show that when in vitro chondrocytes are exposed to higher concentrations of TXA, such as that expected following recommended intra-articular administration, cytotoxicity is observed. This effect is dose-dependent, such that a tissue concentration of 10 mg/ml to 20 mg/ml could be expected to be safe. Cite this article: Bone Joint J 2018;100-B:404–12


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 5 | Pages 691 - 699
1 May 2009
Amin AK Huntley JS Simpson AHRW Hall AC

The aim of this study was to determine whether subchondral bone influences in situ chondrocyte survival. Bovine explants were cultured in serum-free media over seven days with subchondral bone excised from articular cartilage (group A), subchondral bone left attached to articular cartilage (group B), and subchondral bone excised but co-cultured with articular cartilage (group C). Using confocal laser scanning microscopy, fluorescent probes and biochemical assays, in situ chondrocyte viability and relevant biophysical parameters (cartilage thickness, cell density, culture medium composition) were quantified over time (2.5 hours vs seven days). There was a significant increase in chondrocyte death over seven days, primarily within the superficial zone, for group A, but not for groups B or C (p < 0.05). There was no significant difference in cartilage thickness or cell density between groups A, B and C (p > 0.05). Increases in the protein content of the culture media for groups B and C, but not for group A, suggested that the release of soluble factors from subchondral bone may have influenced chondrocyte survival. In conclusion, subchondral bone significantly influenced chondrocyte survival in articular cartilage during explant culture. The extrapolation of bone-cartilage interactions in vitro to the clinical situation must be made with caution, but the findings from these experiments suggest that future investigation into in vivo mechanisms of articular cartilage survival and degradation must consider the interactions of cartilage with subchondral bone


Bone & Joint Research
Vol. 7, Issue 5 | Pages 336 - 342
1 May 2018
Hotham WE Malviya A

This systematic review examines the current literature regarding surgical techniques for restoring articular cartilage in the hip, from the older microfracture techniques involving perforation to the subchondral bone, to adaptations of this technique using nanofractures and scaffolds. This review discusses the autologous and allograft transfer systems and the autologous matrix-induced chondrogenesis (AMIC) technique, as well as a summary of the previously discussed techniques, which could become common practice for restoring articular cartilage, thus reducing the need for total hip arthroplasty. Using the British Medical Journal Grading of Recommendations, Assessment, Development and Evaluation (BMJ GRADE) system and Grade system. Comparison of the studies discussed shows that microfracture has the greatest quantity and quality of research, whereas the newer AMIC technique requires more research, but shows promise. Cite this article: W. E. Hotham, A. Malviya. A systematic review of surgical methods to restore articular cartilage in the hip. Bone Joint Res 2018;7:336–342. DOI: 10.1302/2046-3758.75.BJR-2017-0331


Bone & Joint Research
Vol. 7, Issue 1 | Pages 20 - 27
1 Jan 2018
Kang K Son J Suh D Kwon SK Kwon O Koh Y

Objectives. Patient-specific (PS) implantation surgical technology has been introduced in recent years and a gradual increase in the associated number of surgical cases has been observed. PS technology uses a patient’s own geometry in designing a medical device to provide minimal bone resection with improvement in the prosthetic bone coverage. However, whether PS unicompartmental knee arthroplasty (UKA) provides a better biomechanical effect than standard off-the-shelf prostheses for UKA has not yet been determined, and still remains controversial in both biomechanical and clinical fields. Therefore, the aim of this study was to compare the biomechanical effect between PS and standard off-the-shelf prostheses for UKA. Methods. The contact stresses on the polyethylene (PE) insert, articular cartilage and lateral meniscus were evaluated in PS and standard off-the-shelf prostheses for UKA using a validated finite element model. Gait cycle loading was applied to evaluate the biomechanical effect in the PS and standard UKAs. Results. The contact stresses on the PE insert were similar for both the PS and standard UKAs. Compared with the standard UKA, the PS UKA did not show any biomechanical effect on the medial PE insert. However, the contact stresses on the articular cartilage and the meniscus in the lateral compartment following the PS UKA exhibited closer values to the healthy knee joint compared with the standard UKA. Conclusion. The PS UKA provided mechanics closer to those of the normal knee joint. The decreased contact stress on the opposite compartment may reduce the overall risk of progressive osteoarthritis. Cite this article: K-T. Kang, J. Son, D-S. Suh, S. K. Kwon, O-R. Kwon, Y-G. Koh. Patient-specific medial unicompartmental knee arthroplasty has a greater protective effect on articular cartilage in the lateral compartment: A Finite Element Analysis. Bone Joint Res 2018;7:20–27. DOI: 10.1302/2046-3758.71.BJR-2017-0115.R2


Bone & Joint Research
Vol. 5, Issue 6 | Pages 218 - 224
1 Jun 2016
Cheng N Guo A Cui Y

Objectives. Recent studies have shown that systemic injection of rapamycin can prevent the development of osteoarthritis (OA)-like changes in human chondrocytes and reduce the severity of experimental OA. However, the systemic injection of rapamycin leads to many side effects. The purpose of this study was to determine the effects of intra-articular injection of Torin 1, which as a specific inhibitor of mTOR which can cause induction of autophagy, is similar to rapamycin, on articular cartilage degeneration in a rabbit osteoarthritis model and to investigate the mechanism of Torin 1’s effects on experimental OA. Methods. Collagenase (type II) was injected twice into both knees of three-month-old rabbits to induce OA, combined with two intra–articular injections of Torin 1 (400 nM). Degeneration of articular cartilage was evaluated by histology using the Mankin scoring system at eight weeks after injection. Chondrocyte degeneration and autophagosomes were observed by transmission electron microscopy. Matrix metallopeptidase-13 (MMP-13) and vascular endothelial growth factor (VEGF) expression were analysed by quantitative RT-PCR (qPCR).Beclin-1 and light chain 3 (LC3) expression were examined by Western blotting. Results. Intra-articular injection of Torin 1 significantly reduced degeneration of the articular cartilage after induction of OA. Autophagosomes andBeclin-1 and LC3 expression were increased in the chondrocytes from Torin 1-treated rabbits. Torin 1 treatment also reduced MMP-13 and VEGF expression at eight weeks after collagenase injection. Conclusion. Our results demonstrate that intra-articular injection of Torin 1 reduces degeneration of articular cartilage in collagenase-induced OA, at least partially by autophagy activation, suggesting a novel therapeutic approach for preventing cartilage degeneration and treating OA. Cite this article: N-T. Cheng, A. Guo, Y-P. Cui. Intra-articular injection of Torin 1 reduces degeneration of articular cartilage in a rabbit osteoarthritis model. Bone Joint Res 2016;5:218–224. DOI: 10.1302/2046-3758.56.BJR-2015-0001


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 12 | Pages 1670 - 1674
1 Dec 2006
Rogers BA Murphy CL Cannon SR Briggs TWR

The weight-bearing status of articular cartilage has been shown to affect its biochemical composition. We have investigated the topographical variation of sulphated glycosaminoglycan (GAG) relative to the DNA content of the chondrocyte in human distal femoral articular cartilage. Paired specimens of distal femoral articular cartilage, from weight-bearing and non-weight-bearing regions, were obtained from 13 patients undergoing above-knee amputation. After papain enzyme digestion, spectrophotometric GAG and fluorometric DNA assays assessed the biochemical composition of the samples. The results were analysed using a paired t-test. Although there were no significant differences in cell density between the regions, the weight-bearing areas showed a significantly higher concentration of GAG relative to DNA when compared with non-weight-bearing areas (p = 0.02). We conclude that chondrocytes are sensitive to their mechanical environment, and that local loading conditions influence the metabolism of the cells and hence the biochemical structure of the tissue


Objectives. Adult mice lacking the transcription factor NFAT1 exhibit osteoarthritis (OA). The precise molecular mechanism for NFAT1 deficiency-induced osteoarthritic cartilage degradation remains to be clarified. This study aimed to investigate if NFAT1 protects articular cartilage (AC) against OA by directly regulating the transcription of specific catabolic and anabolic genes in articular chondrocytes. Methods. Through a combined approach of gene expression analysis and web-based searching of NFAT1 binding sequences, 25 candidate target genes that displayed aberrant expression in Nfat1. -/-. AC at the initiation stage of OA, and possessed at least four NFAT1 binding sites in the promoter of each gene, were selected and tested for NFAT1 transcriptional activities by chromatin immunoprecipitation (ChIP) and promoter luciferase reporter assays using chondrocytes isolated from the AC of three- to four-month-old wild-type mice or Nfat1. -/-. mice with early OA phenotype. Results. Chromatin immunoprecipitation assays revealed that NFAT1 bound directly to the promoter of 21 of the 25 tested genes encoding cartilage-matrix proteins, growth factors, inflammatory cytokines, matrix-degrading proteinases, and specific transcription factors. Promoter luciferase reporter assays of representative anabolic and catabolic genes demonstrated that NFAT1-DNA binding functionally regulated the luciferase activity of specific target genes in wild-type chondrocytes, but not in Nfat1. -/-. chondrocytes or in wild-type chondrocytes transfected with plasmids containing mutated NFAT1 binding sequences. Conclusion. NFAT1 protects AC against degradation by directly regulating the transcription of target genes in articular chondrocytes. NFAT1 deficiency causes defective transcription of specific anabolic and catabolic genes in articular chondrocytes, leading to increased matrix catabolism and osteoarthritic cartilage degradation. Cite this article: M. Zhang, Q. Lu, T. Budden, J. Wang. NFAT1 protects articular cartilage against osteoarthritic degradation by directly regulating transcription of specific anabolic and catabolic genes. Bone Joint Res 2019;8:90–100. DOI: 10.1302/2046-3758.82.BJR-2018-0114.R1


Bone & Joint Research
Vol. 7, Issue 3 | Pages 205 - 212
1 Mar 2018
Lin Y Hall AC Simpson AHRW

Objectives. The purpose of this study was to create a novel ex vivo organ culture model for evaluating the effects of static and dynamic load on cartilage. Methods. The metatarsophalangeal joints of 12 fresh cadaveric bovine feet were skinned and dissected aseptically, and cultured for up to four weeks. Dynamic movement was applied using a custom-made machine on six joints, with the others cultured under static conditions. Chondrocyte viability and matrix glycosaminoglycan (GAG) content were evaluated by the cell viability probes, 5-chloromethylfluorescein diacetate (CMFDA) and propidium iodide (PI), and dimethylmethylene blue (DMMB) assay, respectively. Results. Chondrocyte viability in the static model decreased significantly from 89.9% (. sd. 2.5%) (Day 0) to 66.5% (. sd. 13.1%) (Day 28), 94.7% (. sd. 1.1%) to 80. 9% (. sd. 5.8%) and 80.1% (. sd. 3.0%) to 46.9% (. sd. 8.5%) in the superficial quarter, central half and deep quarter of cartilage, respectively (p < 0.001 in each zone; one-way analysis of variance). The GAG content decreased significantly from 6.01 μg/mg (. sd. 0.06) (Day 0) to 4.71 μg/mg (. sd. 0.06) (Day 28) (p < 0.001; one-way analysis of variance). However, with dynamic movement, chondrocyte viability and GAG content were maintained at the Day 0 level over the four-week period without a significant change (chondrocyte viability: 92.0% (. sd. 4.0%) (Day 0) to 89.9% (. sd. 0.2%) (Day 28), 93.1% (. sd. 1.5%) to 93.8% (. sd. 0.9%) and 85.6% (. sd. 0.8%) to 84.0% (. sd. 2.9%) in the three corresponding zones; GAG content: 6.18 μg/mg (. sd. 0.15) (Day 0) to 6.06 μg/mg (. sd. 0.09) (Day 28)). Conclusion. Dynamic joint movement maintained chondrocyte viability and cartilage GAG content. This long-term whole joint culture model could be of value in providing a more natural and controlled platform for investigating the influence of joint movement on articular cartilage, and for evaluating novel therapies for cartilage repair. Cite this article: Y-C. Lin, A. C. Hall, A. H. R. W. Simpson. A novel organ culture model of a joint for the evaluation of static and dynamic load on articular cartilage. Bone Joint Res 2018;7:205–212. DOI: 10.1302/2046-3758.73.BJR-2017-0320


The Journal of Bone & Joint Surgery British Volume
Vol. 91-B, Issue 5 | Pages 565 - 576
1 May 2009
Getgood A Brooks R Fortier L Rushton N

Articular cartilage repair remains a challenge to surgeons and basic scientists. The field of tissue engineering allows the simultaneous use of material scaffolds, cells and signalling molecules to attempt to modulate the regenerative tissue. This review summarises the research that has been undertaken to date using this approach, with a particular emphasis on those techniques that have been introduced into clinical practice, via in vitro and preclinical studies


The Journal of Bone & Joint Surgery British Volume
Vol. 50-B, Issue 1 | Pages 198 - 215
1 Feb 1968
Urist MR Adams T

1. Isografts of articular cartilage of young rats, with mucoproteins labelled with . 35. S, extracellular fibrous proteins labelled with . 3. H-glycine, and nuclei labelled with . 3. H-thymidine, were transplanted into the anterior chamber of the eye. 2. Thin split-thickness transplants of the cells of the gliding surface of immature articular cartilage induced the formation of fibrous tissue. 3. Thick transplants and subsurface slices of immature articular cartilage, containing germinal cells of the epiphysial cartilage, induced the formation of new bone consistently within 4 weeks. 4. Full-thickness transplants in articular cartilage from senile rats induced only the formation of fibrous tissue. 5. Slices of growing cartilage, devitalised by cryolysis, or extraction of acid-soluble proteins, produced scanty deposits of bone or cartilage, or both, but only infrequently and generally after a lag phase extending from six to twelve weeks. 6. Reduction in the amount of mucoprotein in the cartilage matrix by papain, and suppression of the resynthesis of tissue proteins by cortisone, retarded but did not prevent bone induction. 7. Bone induction is the product of a series of interactions between inducing cells and responding cells by intracellular and intercellular reactions too complex to characterise in physico-chemical terms at this time


The Journal of Bone & Joint Surgery British Volume
Vol. 93-B, Issue 2 | Pages 277 - 284
1 Feb 2011
Amin AK Huntley JS Patton JT Brenkel IJ Simpson AHRW Hall AC

The aim of this study was to determine whether exposure of human articular cartilage to hyperosmotic saline (0.9%, 600 mOsm) reduces in situ chondrocyte death following a standardised mechanical injury produced by a scalpel cut compared with the same assault and exposure to normal saline (0.9%, 285 mOsm). Human cartilage explants were exposed to normal (control) and hyperosmotic 0.9% saline solutions for five minutes before the mechanical injury to allow in situ chondrocytes to respond to the altered osmotic environment, and incubated for a further 2.5 hours in the same solutions following the mechanical injury. Using confocal laser scanning microscopy, we identified a sixfold (p = 0.04) decrease in chondrocyte death following mechanical injury in the superficial zone of human articular cartilage exposed to hyperosmotic saline compared with normal saline. These data suggest that increasing the osmolarity of joint irrigation solutions used during open and arthroscopic articular surgery may reduce chondrocyte death from surgical injury and could promote integrative cartilage repair


The Journal of Bone & Joint Surgery British Volume
Vol. 57-B, Issue 4 | Pages 525 - 528
1 Nov 1975
Lutfi AM

The medial meniscus was resected from the right knees of twelve young grivet monkeys that were killed at intervals of twenty-one to 252 days after operation. The knees operated upon and the control knees were investigated radiologically and histologically. Degenerative changes occurred in the medial femoral and tibial condyles. At first there was loss of cells from the superficial layer of the articular cartilage, with a marked decrease in the acid mucopolysaccharide content of the matrix. The chondrocytes in the deeper layer of the non-calcified zone proliferated to form clones before finally degenerating. The acellular cartilage showed splitting, and with progress of the degenerative process there was thinning and erosion of the cartilage. Eventually there was complete loss of articular cartilage with thickening and exposure of the subchondral bone. These degenerative changes were confined to a small area of the articular cartilage and had occurred despite regeneration of the meniscus. The rest of the cartilage looked normal. It is concluded that articular cartilage deprived of the protection of a meniscus may undergo arthritic changes


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 9 | Pages 1285 - 1291
1 Sep 2005
Whiteside RA Jakob RP Wyss UP Mainil-Varlet P

Surgical reconstruction of articular surfaces by transplantation of osteochondral autografts has shown considerable promise in the treatment of focal articular lesions. During mosaicplasty, each cylindrical osteochondral graft is centred over the recipient hole and delivered by impacting the articular surface. Impact loading of articular cartilage has been associated with structural damage, loss of the viability of chondrocytes and subsequent degeneration of the articular cartilage. We have examined the relationship between single-impact loading and chondrocyte death for the specific confined-compression boundary conditions of mosaicplasty and the effect of repetitive impact loading which occurs during implantation of the graft on the resulting viability of the chondrocytes. Fresh bovine and porcine femoral condyles were used in this experiment. The percentage of chondrocyte death was found to vary logarithmically with single-impact energy and was predicted more strongly by the mean force of the impact rather than by the number of impacts required during placement of the graft. The significance of these results in regard to the surgical technique and design features of instruments for osteochondral transplantation is discussed


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 7 | Pages 1033 - 1040
1 Jul 2010
Nishino T Chang F Ishii T Yanai T Mishima H Ochiai N

We have previously shown that joint distraction and movement with a hinged external fixation device for 12 weeks was useful for repairing a large articular cartilage defect in a rabbit model. We have now investigated the results after six months and one year. The device was applied to 16 rabbits who underwent resection of the articular cartilage and subchondral bone from the entire tibial plateau. In group A (nine rabbits) the device was applied for six months. In group B (seven rabbits) it was in place for six months, after which it was removed and the animals were allowed to move freely for an additional six months. The cartilage remained sound in all rabbits. The areas of type II collagen-positive staining and repaired soft tissue were larger in group B than in group A. These findings provide evidence of long-term persistence of repaired cartilage with this technique and that weight-bearing has a positive effect on the quality of the cartilage


The Journal of Bone & Joint Surgery British Volume
Vol. 56-B, Issue 1 | Pages 167 - 177
1 Feb 1974
Sengupta S

1. Articular cartilage from immature rabbits was placed in and near the rabbit knee joints for periods up to ten weeks. 2. Autografts of articular cartilage when placed free in the joint soon became adherent to its synovial lining; the cartilage with its subchondral bone remained viable. 3. Homografts remained viable in the presence of joint fluid, but when in contact with synovium antigenic cellular reaction was produced early. The presence of subchondral bone intensified this reaction and led to graft invasion and destruction. 4. Partial thickness homografts of articular cartilage were also antigenic and were absorbed. When full thickness cartilage was used, this cellular invasion was resisted by the zone of provisional calcification which appeared to function as a physical barrier against antigenic cells of the host. 5. When placed in muscle, both autogenous and homogenous grafts failed to survive through lack of nutrition, although the autogenous subchondral bone remained viable. It is inferred that subchondral circulation is not sufficient for cartilage survival and synovial fluid is essential for its proper nutrition. 6. Surviving immature articular cartilage transplants underwent "ageing" changes


The Journal of Bone & Joint Surgery British Volume
Vol. 53-B, Issue 3 | Pages 541 - 548
1 Aug 1971
Repo RU Mitchell N

1. The utilisation of labelled proline in normal and injured mature rabbit articular cartilage has been studied and compared simultaneously in one phase of the study with radiosulphate utilisation. The morphologic features of lacerative injury paralleled those reported previously. 2. Labelled proline is actively utilised by mature articular cartilage and can be recovered in time from the matrix as labelled hydroxyproline. This is taken as evidence of collagen synthesis. 3. Evidence is presented to suggest that the rate of formation of labelled hydroxyproline may be augmented after lacerative trauma. 4. Parallel utilisation of radiosulphate and labelled proline suggests that the synthesis of chondromucoprotein and collagen are closely related and that the continual synthesis of both moieties is necessary for the maintenance of normal matrix. 5. Despite evidence of increased chondromucoprotein and collagen synthesis no significant contribution is made to the healing of lacerative defects in mature rabbit articular cartilage


Bone & Joint Research
Vol. 7, Issue 7 | Pages 457 - 467
1 Jul 2018
Smith IDM Milto KM Doherty CJ Amyes SGB Simpson AHRW Hall AC

Objectives. Staphylococcus aureus (S. aureus) is the most commonly implicated organism in septic arthritis, a condition that may be highly destructive to articular cartilage. Previous studies investigating laboratory and clinical strains of S. aureus have demonstrated that potent toxins induced significant chondrocyte death, although the precise toxin or toxins that were involved was unknown. In this study, we used isogenic S. aureus mutants to assess the influence of alpha (Hla)-, beta (Hlb)-, and gamma (Hlg)-haemolysins, toxins considered important for the destruction of host tissue, on in situ bovine chondrocyte viability. Methods. Bovine cartilage explants were cultured with isogenic S. aureus mutants and/or their culture supernatants. Chondrocyte viability was then assessed within defined regions of interest in the axial and coronal plane following live- and dead-cell imaging using the fluorescent probes 5-chloromethylfluorescein diacetate and propidium iodide, respectively, and confocal laser-scanning microscopy. Results. Hla-producing mutants caused substantial chondrocyte death compared with the toxin-deficient control (Hla-Hlb-Hlg-), whilst mutants producing Hlb and Hlg in the absence of Hla induced minimal chondrocyte death. Coronal studies established that Hla-induced chondrocyte death started in the superficial zone of cartilage and spread to deeper layers, whereas Hlb and Hlg toxins were without significant effect. Conclusion. This study identified Hla as a highly potent S. aureus toxin that caused rapid chondrocyte death in bovine cartilage, with other toxins or metabolic products produced by the bacteria playing a minor role. The identification of Hla in mediating chondrocyte death may assist in the development of therapeutic strategies aimed at reducing the extent of cartilage damage during and after an episode of septic arthritis. Cite this article: I. D. M. Smith, K. M. Milto, C. J. Doherty, S. G. B. Amyes, A. H. R. W. Simpson, A. C. Hall. A potential key role for alpha-haemolysin of Staphylococcus aureus in mediating chondrocyte death in septic arthritis. Bone Joint Res 2018;7:457–467. DOI: 10.1302/2046-3758.77.BJR-2017-0165.R1


The Journal of Bone & Joint Surgery British Volume
Vol. 50-B, Issue 4 | Pages 852 - 857
1 Nov 1968
Bullough P Goodfellow J

The collagen framework of articular cartilage is disposed, as in other connective tissues, to resist tension forces within the material. In this paper the fine structure of articular cartilage, as demonstrated by polarised light microscopy and electron microscopy, is related to the gross anatomy and to the naked eye changes of chondromalacia and fibrillation


Bone & Joint Research
Vol. 5, Issue 11 | Pages 560 - 568
1 Nov 2016
Peeters M Huang CL Vonk LA Lu ZF Bank RA Helder MN Doulabi BZ

Objectives. Studies which consider the molecular mechanisms of degeneration and regeneration of cartilaginous tissues are seriously hampered by problematic ribonucleic acid (RNA) isolations due to low cell density and the dense, proteoglycan-rich extracellular matrix of cartilage. Proteoglycans tend to co-purify with RNA, they can absorb the full spectrum of UV light and they are potent inhibitors of polymerase chain reaction (PCR). Therefore, the objective of the present study is to compare and optimise different homogenisation methods and RNA isolation kits for an array of cartilaginous tissues. Materials and Methods. Tissue samples such as the nucleus pulposus (NP), annulus fibrosus (AF), articular cartilage (AC) and meniscus, were collected from goats and homogenised by either the MagNA Lyser or Freezer Mill. RNA of duplicate samples was subsequently isolated by either TRIzol (benchmark), or the RNeasy Lipid Tissue, RNeasy Fibrous Tissue, or Aurum Total RNA Fatty and Fibrous Tissue kits. RNA yield, purity, and integrity were determined and gene expression levels of type II collagen and aggrecan were measured by real-time PCR. Results. No differences between the two homogenisation methods were found. RNA isolation using the RNeasy Fibrous and Lipid kits resulted in the purest RNA (A260/A280 ratio), whereas TRIzol isolations resulted in RNA that is not as pure, and show a larger difference in gene expression of duplicate samples compared with both RNeasy kits. The Aurum kit showed low reproducibility. Conclusion. For the extraction of high-quality RNA from cartilaginous structures, we suggest homogenisation of the samples by the MagNA Lyser. For AC, NP and AF we recommend the RNeasy Fibrous kit, whereas for the meniscus the RNeasy Lipid kit is advised. Cite this article: M. Peeters, C. L. Huang, L. A. Vonk, Z. F. Lu, R. A. Bank, M. N. Helder, B. Zandieh Doulabi. Optimisation of high-quality total ribonucleic acid isolation from cartilaginous tissues for real-time polymerase chain reaction analysis. Bone Joint Res 2016;5:560–568. DOI: 10.1302/2046-3758.511.BJR-2016-0033.R3


The Journal of Bone & Joint Surgery British Volume
Vol. 51-B, Issue 4 | Pages 747 - 753
1 Nov 1969
Greenwald AS Haynes DW

1. The routes by which adult human articular cartilage can receive its nutrition is still a subject of controversy. 2. Microscopic examination of normal adult human femoral heads has revealed vascular channels which penetrate the subchondral plate and calcified cartilage. These channels bring the medullary soft tissue into contact with the articular cartilage. 3. A fluorescent dye migration technique was used to show that the observed vascular channels are pathways for dye from the medullary cavity to the articular cartilage. It is suggested that these pathways could also be routes by which articular cartilage receives part of its nutrition. 4. The nutritional mechanism in the mature rabbit and adult human femoral heads cannot be compared because histological studies revealed differences in their subchondral structures


The Journal of Bone & Joint Surgery British Volume
Vol. 55-B, Issue 3 | Pages 588 - 594
1 Aug 1973
Rothwell AG Bentley G

1. Twelve trephine specimens of articular cartilage and subchondral bone taken from six fresh osteoarthritic femoral heads were incubated in a medium containing tritiated thymidine, and autoradiographs were prepared from serial sections five microns thick. 2. Scattered labelling of chondrocytes in sections from four of the six femoral heads was demonstrated. No more than four labelled cells were seen in any one section. About half were found in typical chondrocyte clusters. 3. The implications of this evidence of chondrocyte multiplication with regard to the repair of damaged articular cartilage are discussed


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 5 | Pages 693 - 700
1 May 2007
Ishii I Mizuta H Sei A Hirose J Kudo S Hiraki Y

We have investigated in vitro the release kinetics and bioactivity of fibroblast growth factor-2 (FGF-2) released from a carrier of fibrin sealant. In order to evaluate the effects of the FGF-2 delivery mechanism on the repair of articular cartilage, full-thickness cylindrical defects, 5 mm in diameter and 4 mm in depth, which were too large to undergo spontaneous repair, were created in the femoral trochlea of rabbit knees. These defects were then filled with the sealant. Approximately 50% of the FGF-2 was released from the sealant within 24 hours while its original bioactivity was maintained. The implantation of the fibrin sealant incorporating FGF-2 successfully induced healing of the surface with hyaline cartilage and concomitant repair of the subchondral bone at eight weeks after the creation of the defect. Our findings suggest that this delivery method for FGF-2 may be useful for promoting regenerative repair of full-thickness defects of articular cartilage in humans


The Journal of Bone & Joint Surgery British Volume
Vol. 52-B, Issue 1 | Pages 108 - 118
1 Feb 1970
Lowe HG

1. Six cases of necrosis of articular cartilage complicating slipping of the upper femoral epiphysis are reviewed: histological examination in one case showed death of the superficial two-thirds of the articular cartilage, with survival of a layer of basal chondrocytes. In all six cases, after severe initial reduction of joint space as seen radiographically, there was gradual return of joint space, suggesting some regeneration of articular cartilage. The prognosis after cartilage necrosis is therefore not always so bad as has been supposed. 2. Various hypotheses concerning the cause of cartilage necrosis complicating slipped epiphysis are reviewed. The precise cause remains unknown, but there is substantial evidence against its being a consequence of ischaemia of the femoral head


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 5 | Pages 721 - 729
1 May 2005
Yanai T Ishii T Chang F Ochiai N

We produced large full-thickness articular cartilage defects in 33 rabbits in order to evaluate the effect of joint distraction and autologous culture-expanded bone-marrow-derived mesenchymal cell transplantation (ACBMT) at 12 weeks. After fixing the knee on a hinged external fixator, we resected the entire surface of the tibial plateau. We studied three groups: 1) with and without joint distraction; 2) with joint distraction and collagen gel, and 3) with joint distraction and ACBMT and collagen gel. The histological scores were significantly higher in the groups with ACBMT collagen gel (p < 0.05). The area of regenerated soft tissue was smaller in the group allowed to bear weight (p < 0.05). These findings suggest that the repair of large defects of cartilage can be enhanced by joint distraction, collagen gel and ACBMT


The Bone & Joint Journal
Vol. 100-B, Issue 5 | Pages 590 - 595
1 May 2018
Sawa M Nakasa T Ikuta Y Yoshikawa M Tsuyuguchi Y Kanemitsu M Ota Y Adachi N

Aims. The aim of this study was to evaluate antegrade autologous bone grafting with the preservation of articular cartilage in the treatment of symptomatic osteochondral lesions of the talus with subchondral cysts. Patients and Methods. The study involved seven men and five women; their mean age was 35.9 years (14 to 70). All lesions included full-thickness articular cartilage extending through subchondral bone and were associated with subchondral cysts. Medial lesions were exposed through an oblique medial malleolar osteotomy, and one lateral lesion was exposed by expanding an anterolateral arthroscopic portal. After refreshing the subchondral cyst, it was grafted with autologous cancellous bone from the distal tibial metaphysis. The fragments of cartilage were fixed with 5-0 nylon sutures to the surrounding cartilage. Function was assessed at a mean follow-up of 25.3 months (15 to 50), using the American Orthopaedic Foot and Ankle Society (AOFAS) ankle-hindfoot outcome score. The radiological outcome was assessed using MRI and CT scans. Results. The mean AOFAS score improved from 65.7 (47 to 81) preoperatively to 92 (90 to 100) at final follow-up, with 100% patient satisfaction. The radiolucent area of the cysts almost disappeared on plain radiographs in all patients immediately after surgery, and there were no recurrences at the most recent follow-up. The medial malleolar screws were removed in seven patients, although none had symptoms. At this time, further arthroscopy was undertaken, when it was found that the mean International Cartilage Repair Society (ICRS) arthroscopic score represented near-normal cartilage. Conclusion. Autologous bone grafting with fixation of chondral fragments preserves the original cartilage in the short term, and could be considered in the treatment for adult patients with symptomatic osteochondral defect and subchondral cysts. Cite this article: Bone Joint J 2018;100-B:590–5


The Journal of Bone & Joint Surgery British Volume
Vol. 73-B, Issue 5 | Pages 795 - 801
1 Sep 1991
Jeffery A Blunn G Archer C Bentley G

The three-dimensional architecture of bovine articular cartilage collagen and its relationship to split lines has been studied with scanning electron microscopy. In the middle and superficial zones, collagen was organised in a layered or leaf-like manner. The orientation was vertical in the intermediate zone, curving to become horizontal and parallel to the articular surface in the superficial zone. Each leaf consisted of a fine network of collagen fibrils. Adjacent leaves merged or were closely linked by bridging fibrils and were arranged according to the split-line pattern. The surface layer (lamina splendens) was morphologically distinct. Although ordered, the overall collagen structure was different in each plane (anisotropic) a property described in previous morphological and biophysical studies. As all components of the articular cartilage matrix interact closely, the three-dimensional organisation of collagen is important when considering cartilage function and the processes of cartilage growth, injury and repair


The Journal of Bone & Joint Surgery British Volume
Vol. 83-B, Issue 7 | Pages 1001 - 1004
1 Sep 2001
Yasunaga Y Ikuta Y Kanazawa T Takahashi K Hisatome T

We have studied whether the state of the articular cartilage at the time of rotational acetabular osteotomy for dysplasia of the hip affects the outcome 2 to 5.5 years after surgery. Arthroscopy in 57 patients (59 joints) at the time of the operation showed grade-0 changes in seven, grade-1 in nine, grade-2 in 17, grade-3 in 14 and grade-4 in 12 joints, according to the classification of Outerbridge. There was radiological evidence of the progression of arthritis in four joints which were classified at arthroscopy as grade 4. Stepwise regression analysis showed that damage to acetabular or femoral articular cartilage significantly affected the progression of arthritis. We conclude that the short-term results of successful rotational acetabular osteotomy for dysplasia are affected by the state of the articular cartilage


The Journal of Bone & Joint Surgery British Volume
Vol. 92-B, Issue 7 | Pages 941 - 948
1 Jul 2010
Stone KR Adelson WS Pelsis JR Walgenbach AW Turek TJ

We describe 119 meniscal allograft transplantations performed concurrently with articular cartilage repair in 115 patients with severe articular cartilage damage. In all, 53 (46.1%) of the patients were over the age of 50 at the time of surgery. The mean follow-up was for 5.8 years (2 months to 12.3 years), with 25 procedures (20.1%) failing at a mean of 4.6 years (2 months to 10.4 years). Of these, 18 progressed to knee replacement at a mean of 5.1 years (1.3 to 10.4). The Kaplan-Meier estimated mean survival time for the whole series was 9.9 years (. sd. 0.4). Cox’s proportional hazards model was used to assess the effect of covariates on survival, with age at the time of surgery (p = 0.026) and number of previous operations (p = 0.006) found to be significant. The survival of the transplant was not affected by gender, the severity of cartilage damage, axial alignment, the degree of narrowing of the joint space or medial versus lateral allograft transplantation. Patients experienced significant improvements at all periods of follow-up in subjective outcome measures of pain, activity and function (all p-values < 0.05), with the exception of the seven-year Tegner index score (p = 0.076)


The Journal of Bone & Joint Surgery British Volume
Vol. 45-B, Issue 1 | Pages 150 - 161
1 Feb 1963
Meachim G

1. The changes resulting from superficial scarification of articular cartilage have been observed in the knee joint of adult rabbits. A reduction in the amount of stainable matrix ground substance occurred at the sites of damage. Particular attention was therefore paid to sulphated mucopolysaccharide synthesis by cartilage cells in or near the traumatised areas. 2. The femoral groove cartilage one week after scarification showed evidence of increased mucopolysaccharide synthesis, especially by the more superficial chondrocytes near the cuts, but three or four weeks later the enhanced chondrocyte activity tended to diminish, and after six weeks the superficial cells near the cuts were found to be inactive. From six to thirty-four weeks the loss of stainable ground substance extended more deeply, but cell degeneration in these deeper areas of matrix depletion was preceded by a period in which many of the deeper chondrocytes still showed evidence of active mucopolysaccharide synthesis. Cellular activity in tags of depleted cartilage was usually lost before the tags finally disintegrated. Chondrocyte clusters were often seen in the scarified areas, especially in the deeper zones. They seemed to be a reactive rather than degenerative phenomenon. 3. In the scarified cartilages of the patella examined after one week a reactive response by superficial chondrocytes was less evident than in the femoral cartilage from the same joint, and after six weeks areas of deeply extending matrix loss were exceptional. 4. The structural and functional changes in the rabbits' femoral articular cartilage after its scarification resembled those which have been observed in the developing cartilage lesion of human osteoarthritis–namely, loss of interstitial matrix and superficial fibrillation, a stimulated synthesis of chondroitin sulphate by the chondrocytes, and the appearance of cell clusters in the deeper zones. Within the period of the experiment, up to thirty-four weeks, the joint lesions remained strictly localised to the traumatised areas ofcartilage, and exposure of bone and joint remodelling, which are features of advanced osteoarthritis in man, were not seen


The Journal of Bone & Joint Surgery British Volume
Vol. 42-B, Issue 3 | Pages 530 - 534
1 Aug 1960
Hosking GE Clennar G

A case of calcification of articular cartilage in association with a parathyroid tumour is described. Previously reported cases of articular calcification are briefly discussed, and it is recommended that patients with articular calcification of undetermined cause should be investigated for hyperparathyroidism


The Journal of Bone & Joint Surgery British Volume
Vol. 38-B, Issue 4 | Pages 874 - 881
1 Nov 1956
Bunjé H Cole WR

1. Idiopathic calcification of articular cartilages is described in a Jamaican woman of thirty-one years who had intermittent joint pains for ten years and who had evidence of past gonococcal infection. She was otherwise normal. 2. The etiology of the condition is unknown. 3. Previous literature is reviewed


The Journal of Bone & Joint Surgery British Volume
Vol. 54-B, Issue 2 | Pages 360 - 370
1 May 1972
Galway RD Cruess RL

Subtotal synovectomy was performed in the knee joints of New Zealand white rabbits. The changes noted in the articular cartilage as manifest by decreased metachromatic staining of the matrix were considered to indicate matrix degradation caused by the altered joint environment. The documentation of the enzyme changes suggests that the histological alteration in the articular cartilage noted after synovectomy may be mediated through the activation of endogenous chondrocyte lysozomal enzymes, particularly cathepsin and acid hydrolases


The Journal of Bone & Joint Surgery British Volume
Vol. 81-B, Issue 6 | Pages 1064 - 1068
1 Nov 1999
Richardson JB Caterson B Evans EH Ashton BA Roberts S

Tissue engineering is an increasingly popular method of addressing pathological disorders of cartilage. Recent studies have demonstrated its clinical efficacy, but there is little information on the structural organisation and biochemical composition of the repair tissue and its relation to the adjacent normal tissue. We therefore analysed by polarised light microscopy and immunohistochemistry biopsies of repair tissue which had been taken 12 months after implantation of autologous chondrocytes in two patients with defects of articular cartilage. Our findings showed zonal heterogeneity throughout the repair tissue. The deeper zone resembled hyaline-like articular cartilage whereas the upper zone was more fibrocartilaginous. The results indicate that within 12 months autologous chondrocyte implantation successfully produces replacement cartilage tissue, a major part of which resembles normal hyaline cartilage


The Journal of Bone & Joint Surgery British Volume
Vol. 51-B, Issue 3 | Pages 529 - 539
1 Aug 1969
Liverpool GM Roy S

1. The surface of mature adult human articular cartilage from the knee has been studied by electron microscopy in eleven patients ranging in age from thirty-seven to eighty-three years. The ultrastructural appearance varies from person to person and often from area to area in the same specimen. These variations range from an intact surface to one showing overt fibrillation visible with the light microscope. 2. In areas where the articular surface appears intact the underlying superficial matrix consists of closely packed collagen fibres with only a small amount of interfibrillary ground substance. The collagen fibres show a predominantly tangential orientation in this region of the cartilage. Osmophilic lipidic bodies are sometimes seen in the matrix very close to the joint surface. 3. The appearances under the electron microscope are altered in what is interpreted as an early ultrastructural change in the development of cartilage fibrillation. In the affected areas the collagen fibres show abnormally wide separation by an excessive amount of interfibrillary matrix. Collagen fibres become directly exposed to the joint cavity, and the surface can also show accumulations of finely granular material and sometimes tuft-like projections containing collagen fibres and fine fibrils. At a slightly later stage shallow clefts and steeply sloping curves are apparent at the surface. It is suggested that these various alterations precede the development of overt fibrillation visible under the light microscope. 4. Electron micrographs occasionally show small "blisters" at the articular surface. Electron microscopy has not given evidence of shedding of cells into the joint cavity from non-fibrillated areas of adult human articular cartilage. Cells can, however, sometimes become exposed at the surface in fibrillated areas


The Journal of Bone & Joint Surgery British Volume
Vol. 87-B, Issue 7 | Pages 1019 - 1023
1 Jul 2005
Shimogaki K Yasunaga Y Ochi M

Acetabular dysplasia was produced in 24 immature white rabbits. A rotational acetabular osteotomy was then carried out and radiological and histological studies of the articular cartilage were made. In the hips which did not undergo osteotomy, radiographs at 26 weeks showed that residual subluxation remained and arthritic changes such as narrowing of the joint space or dislocation were still seen. However, in the operated group there was a remarkable increase in cover, but arthritic changes were not observed. After 24 weeks, the Mankin grading score in the operated group was significantly lower than that in the non-operated group. The latter hips showed an irregular surface of the cartilage, exfoliation and proliferation of synovial tissue. In those undergoing osteotomy, primary cloning of chondrocytes or hypercellularity was seen and at 24 weeks after operation and metaplasia of the cartilage in the fibrous tissue was observed in the boundary between the medial area of the acetabulum and the acetabular fossa


The Journal of Bone & Joint Surgery British Volume
Vol. 65-B, Issue 1 | Pages 72 - 78
1 Jan 1983
Bullough P Jagannath A

Biochemical and histochemical studies have indicated that there is specific cellular activity in the region of the calcification front of articular cartilage implying that a regulation process takes place there. Using scanning and transmission electron microscopy and light microscopy to examine tissue sections of both undecalcified and decalcified articular cartilage in the region of the calcification front, we have looked at its morphology with particular reference to its cellular control. Our observations show that physiological calcification is an active process under cellular control and is related to the presence of extracellular membrane-bound matrix vesicles


The Journal of Bone & Joint Surgery British Volume
Vol. 46-B, Issue 3 | Pages 530 - 538
1 Aug 1964
Crock HV

1. Sixteen patients with articular cartilage erosions after slight injury have been described, as have the results of their treatment. 2. The clinical features of this rarely diagnosed condition are discussed. Attention is drawn to "articular crepitus" and "synovial crepitus" as useful physical signs in establishing the diagnosis. 3. A radiographic sign of localised subarticular osteoporosis is reported and discussed. 4. The surgical treatment used was either shaving of the affected area of cartilage or a combination of shaving with drilling of the subchondral bone plate


The Journal of Bone & Joint Surgery British Volume
Vol. 88-B, Issue 11 | Pages 1528 - 1532
1 Nov 2006
Pun SY Teng MS Kim HT

Desiccation of articular cartilage during surgery is often unavoidable and may result in the death of chondrocytes, with subsequent joint degeneration. This study was undertaken to determine the extent of chondrocyte death caused by exposure to air and to ascertain whether regular rewetting of cartilage could decrease cell death. Macroscopically normal human cartilage was exposed to air for 0, 30, 60 or 120 minutes. Selected samples were wetted in lactated Ringer’s solution for ten seconds every ten or 20 minutes. The viability of chondrocytes was measured after three days by Live/Dead staining. Chondrocyte death correlated with the length of exposure to air and the depth of the cartilage. Drying for 120 minutes caused extensive cell death mainly in the superficial 500 μm of cartilage. Rewetting every ten or 20 minutes significantly decreased cell death. The superficial zone is most susceptible to desiccation. Loss of superficial chondrocytes likely decreases the production of essential lubricating glycoproteins and contributes to subsequent degeneration. Frequent wetting of cartilage during arthrotomy is therefore essential


Bone & Joint Research
Vol. 5, Issue 7 | Pages 294 - 300
1 Jul 2016
Nishioka H Nakamura E Hirose J Okamoto N Yamabe S Mizuta H

Objectives. The purpose of this study was to clarify the appearance of the reparative tissue on the articular surface and to analyse the properties of the reparative tissue after hemicallotasis osteotomy (HCO) using MRI T1ρ and T2 mapping. Methods. Coronal T1ρ and T2 mapping and three-dimensional gradient-echo images were obtained from 20 subjects with medial knee osteoarthritis. We set the regions of interest (ROIs) on the full-thickness cartilage of the medial femoral condyle (MFC) and medial tibial plateau (MTP) of the knee and measured the cartilage thickness (mm) and T1ρ and T2 relaxation times (ms). Statistical analysis of time-dependent changes in the cartilage thickness and the T1ρ and T2 relaxation times was performed using one-way analysis of variance, and Scheffe’s test was employed for post hoc multiple comparison. Results. The cartilage-like repair tissue appeared on the cartilage surface of the medial compartment post-operatively, and the cartilage thickness showed a significant increase between the pre-operative and one-year post-operative time points (MFC; p = 0.003, MTP; p < 0.001). The T1ρ values of the cartilage-like repair tissue showed no difference over time, however, the T2 values showed a significant decrease between the pre-operative and one-year post-operative time points (MFC; p = 0.004, MTP; p = 0.040). Conclusion. This study clarified that the fibrocartilage-like repair tissue appeared on the articular surface of the medial compartment after HCO as evidenced by MRI T1ρ and T2 mapping. Cite this article: H. Nishioka, E. Nakamura, J. Hirose, N. Okamoto, S. Yamabe, H. Mizuta. MRI T1ρ and T2 mapping for the assessment of articular cartilage changes in patients with medial knee osteoarthritis after hemicallotasis osteotomy. Bone Joint Res 2016;5:294–300. DOI: 10.1302/2046-3758.57.BJR-2016-0057.R1


The Journal of Bone & Joint Surgery British Volume
Vol. 67-B, Issue 1 | Pages 42 - 43
1 Jan 1985
Johnson-Nurse C Dandy D

Seventy-six knees with fracture-separations of articular cartilage are described. The lesion involved the full thickness of the articular surface with exposed subchondral bone in 28 knees and only part of the thickness in 48. The clinical features and distribution of the lesions within the knee are described


The Journal of Bone & Joint Surgery British Volume
Vol. 89-B, Issue 7 | Pages 977 - 983
1 Jul 2007
Lee JH Prakash KVB Pengatteeri YH Park SE Koh HS Han CW

We attempted to repair full-thickness defects in the articular cartilage of the trochlear groove of the femur in 30 rabbit knee joints using allogenic cultured chondrocytes embedded in a collagen gel. The repaired tissues were examined at 2, 4, 8, 12 and 24 weeks after operation using histological and histochemical methods. The articular defect filling index measurement was derived from safranin-O stained sections. Apoptotic cellular fractions were derived from analysis of apoptosis in situ using TUNEL staining, and was confirmed using caspase-3 staining along with quantification of the total cellularity. The mean articular defect filling index decreased with time. After 24 weeks it was 0.7 (. sd. 0.10), which was significantly lower than the measurements obtained earlier (p < 0.01). The highest mean percentage of apoptotic cells were observed at 12 weeks, although the total cellularity decreased with time. Because apoptotic cell death may play a role in delamination after chondrocyte transplantation, anti-apoptotic gene therapy may protect transplanted chondrocytes from apoptosis


The Journal of Bone & Joint Surgery British Volume
Vol. 66-B, Issue 4 | Pages 592 - 597
1 Aug 1984
Cruess R Kwok D Duc P Lecavalier M Dang G

Hemiarthroplasty of the hip and some other joints has been used for many years with satisfactory results, but the fate of articular cartilage when weight-bearing against metal has not been reported. Replacement of the head of the femur was carried out in one hip of each of 26 dogs, and the changes in acetabular cartilage studied at intervals of up to 24 weeks. There was early loss of proteoglycan, followed by surface damage to the cartilage, progressive degenerative changes, and growth of pannus from the articular margins. At 24 weeks after operation there was little remaining articular cartilage, while intense subchondral activity suggested that the bony skeleton was being remodelled to conform to the shape of the prosthesis. This study is not intended to suggest that hemiarthroplasty does not help patients


The Journal of Bone & Joint Surgery British Volume
Vol. 43-B, Issue 2 | Pages 376 - 386
1 May 1961
Trias A

The effects on articular cartilage of continuous and intermittent excessive pressures have been studied in the knees of rabbits. Severe degenerative changes in the cartilage were observed; these resembled the typical lesions seen in osteoarthritis in man. They included fibrillation of cartilage, death of chondrocytes, eburnation of joint surfaces, sclerosis of bone and the production of "bone cysts." Regeneration of cartilage was common and it was brought about either by the deeply situated chondrocytes which had escaped death or by metaplasia of young connective tissue cells of the bone marrow