Objectives. As one of the heat-stable enterotoxins, Staphylococcal enterotoxin C2 (SEC2) is synthesized by Staphylococcus aureus, which has been proved to inhibit the growth of tumour cells, and is used as an antitumour agent in cancer immunotherapy. Although SEC2 has been reported to promote osteogenic differentiation of human mesenchymal stem cells (MSCs), the in vivo function of SCE2 in animal model remains elusive. The aim of this study was to further elucidate the in vivo effect of SCE2 on fracture healing. Materials and Methods. Rat MSCs were used to test the effects of SEC2 on their proliferation and osteogenic differentiation potentials. A rat femoral fracture model was used to examine the effect of local administration of SEC2 on fracture healing using radiographic analyses, micro-CT analyses, biomechanical testing, and histological analyses. Results. While SEC2 was found to have no effect on rat MSCs proliferation, it promoted the osteoblast differentiation of rat MSCs. In the rat femoral fracture model, the local administration of SEC2 accelerated fracture healing by increasing fracture callus volumes, bone volume over total volume (BV/TV), and biomechanical recovery. The SEC2 treatment group has superior histological appearance compared with the control group. Conclusion. These data suggest that local administration of SEC2 may be a novel therapeutic approach to enhancing bone repair such as fracture healing. Cite this article: T. Wu, J. Zhang, B. Wang, Y. Sun, Y. Liu, G. Li. Staphylococcal enterotoxin C2 promotes osteogenesis of mesenchymal stem cells and accelerates fracture healing. Bone Joint
Objectives. Degenerative disc disease (DDD) and osteoarthritis (OA) are relatively frequent causes of disability amongst the elderly; they constitute serious socioeconomic costs and significantly impair quality of life. Previous studies to date have found that aggrecan variable number of tandem repeats (VNTR) contributes both to DDD and OA. However, current data are not consistent across studies. The purpose of this study was to evaluate systematically the relationship between aggrecan VNTR, and DDD and/or OA. Methods. This study used a highly sensitive search strategy to identify all published studies related to the relationship between aggrecan VNTR and both DDD and OA in multiple databases from January 1996 to December 2016. All identified studies were systematically evaluated using specific inclusion and exclusion criteria. Cochrane methodology was also applied to the results of this study. Results. The final selection of seven studies was comprehensively evaluated and includes results for 2928 alleles. The most frequent allele among all the studies was allele 27. After comparing the distributions of each allele with others, statistically significant differences have been found in the distribution of the alleles by the two groups, with an over-representation of allele (A)21 (disease: 3.22%, control: 0.44%). Thus, carrying A21 increased the risk of DDD. Such an association was not found to be statistically significant when considering the risk of OA. Conclusions. The findings suggest that VNTR A21 seems to be associated with higher risk to DDD, however, such an association may not be statistically significant regarding the risk of OA. Cite this article: L. Cong, G. Tu, D. Liang. A systematic review of the relationship between the distributions of aggrecan gene VNTR polymorphism and degenerative disc disease/osteoarthritis. Bone Joint
Objectives. In this study, we compared the pain behaviour and osteoarthritis (OA) progression between anterior cruciate ligament transection (ACLT) and osteochondral injury in surgically-induced OA rat models. Methods. OA was induced in the knee joints of male Wistar rats using transection of the ACL or induction of osteochondral injury. Changes in the percentage of high limb weight distribution (%HLWD) on the operated hind limb were used to determine the pain behaviour in these models. The development of OA was assessed and compared using a histological evaluation based on the Osteoarthritis Research Society International (OARSI) cartilage OA histopathology score. Results. Both models showed an increase in joint pain as indicated by a significant (p < 0.05) decrease in the values of %HLWD at one week post-surgery. In the osteochondral injury model, the %HLWD returned to normal within three weeks, while in the ACLT model, a significant decrease in the %HLWD was persistent over an eight-week period. In addition, OA progression was more advanced in the ACLT model than in the osteochondral injury model. Furthermore, the ACLT model exhibited a higher mean OA score than that of the osteochondral injury model at 12 weeks. Conclusion. The development of pain patterns in the ACLT and osteochondral injury models is different in that the OA progression was significant in the ACLT model. Although both can be used as models for a post-traumatic injury of the knee, the selection of appropriate models for OA in preclinical studies should be specified and relevant to the clinical scenario. Cite this article: T. Tawonsawatruk, O. Sriwatananukulkit, W. Himakhun, W. Hemstapat. Comparison of pain behaviour and osteoarthritis progression between anterior cruciate ligament transection and osteochondral injury in rat models. Bone Joint
Surface replacement arthroplasty (SRA), compared with traditional total hip arthroplasty (THA), is more expensive and carries unique concern related to metal ions production and hypersensitivity. Additionally, SRA is a more demanding procedure with a decreased margin for error compared with THA. To justify its use, SRA must demonstrate comparable component survival and some clinical advantages. We therefore performed a systematic literature review to investigate the differences in complication rates, patient-reported outcomes, stress shielding, and hip biomechanics between SRA and THA. A systematic review of the literature was completed using MEDLINE and EMBASE search engines. Inclusion criteria were level I to level III articles that reported clinical outcomes following primary SRA compared with THA. An initial search yielded 2503 potential articles for inclusion. Exclusion criteria included review articles, level IV or level V evidence, less than one year’s follow-up, and previously reported data. In total, 27 articles with 4182 patients were available to analyze.Aims
Materials and Methods
The aim of this systematic review and meta-analysis is to evaluate differences in functional outcomes and complications between single- (SI) and double-incision (DI) techniques for the treatment of distal biceps tendon rupture. A comprehensive search on PubMed, MEDLINE, Scopus, and Cochrane Central databases was conducted to identify studies reporting comparative results of the SI versus the DI approach. The Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) statement was used for search strategy. Of 606 titles, 13 studies met the inclusion criteria; methodological quality was assessed with the Newcastle-Ottawa scale. Random- and fixed-effects models were used to find differences in outcomes between the two surgical approaches. The range of motion (ROM) and the Disabilities of the Arm, Shoulder and Hand (DASH) scores, as well as neurological and non-neurological complications, were assessed.Aims
Methods
Objectives. Secondary fracture healing is strongly influenced by the stiffness of the bone-fixator system. Biomechanical tests are extensively used to investigate stiffness and strength of fixation devices. The stiffness values reported in the literature for locked plating, however, vary by three orders of magnitude. The aim of this study was to examine the influence that the method of restraint and load application has on the stiffness produced, the strain distribution within the bone, and the stresses in the implant for locking plate constructs. Methods. Synthetic composite bones were used to evaluate experimentally the influence of four different methods of loading and restraining specimens, all used in recent previous studies. Two plate types and three screw arrangements were also evaluated for each loading scenario. Computational models were also developed and validated using the experimental tests. Results. The method of loading was found to affect the gap stiffness strongly (by up to six times) but also the magnitude of the plate stress and the location and magnitude of strains at the bone-screw interface. Conclusions. This study demonstrates that the method of loading is responsible for much of the difference in reported stiffness values in the literature. It also shows that previous contradictory findings, such as the influence of working length and very large differences in failure loads, can be readily explained by the choice of loading condition. Cite this article: A. MacLeod, A. H. R. W. Simpson, P. Pankaj. Experimental and numerical investigation into the influence of loading conditions in biomechanical testing of locking plate fracture fixation devices. Bone Joint
Aim. It has been suggested that the use of a pilot-hole may reduce the risk of fracture to the lateral cortex. Therefore the purpose of this study was to determine the effect of a pilot hole on the strains and occurrence of fractures at the lateral cortex during the opening of a high tibial osteotomy (HTO) and post-surgery loading. Materials and Methods. A total of 14 cadaveric tibias were randomized to either a pilot hole (n = 7) or a no-hole (n = 7) condition. Lateral cortex strains were measured while the osteotomy was opened 9 mm and secured in place with a locking plate. The tibias were then subjected to an initial 800 N load that increased by 200 N every 5000 cycles, until failure or a maximum load of 2500 N. Results. There was no significant difference in the strains on the lateral cortex during HTO opening between the pilot hole and no-hole conditions. Similarly, the lateral cortex and fixation plate strains were not significantly different during cyclic loading between the two conditions. Using a pilot hole did not significantly decrease the strains experienced at the lateral cortex, nor did it reduce the risk of fracture. Conclusions. The nonsignificant differences found here most likely occurred because the pilot hole merely translated the stress concentration laterally to a parallel point on the surface of the hole. Cite this article: K. Bujnowski, A. Getgood, K. Leitch, J. Farr, C. Dunning, T. A. Burkhart. A pilot hole does not reduce the strains or risk of fracture to the lateral cortex during and following a medial opening wedge high tibial osteotomy in cadaveric specimens. Bone Joint
Objectives. The primary aim of this study was to assess the reproducibility of the recalled preoperative Oxford Hip Score (OHS) and Oxford Knee Score (OKS) one year following arthroplasty for a cohort of patients. The secondary aim was to assess the reliability of a patient’s recollection of their own preoperative OHS and OKS one year following surgery. Methods. A total of 335 patients (mean age 72.5; 22 to 92; 53.7% female) undergoing total hip arthroplasty (n = 178) and total knee arthroplasty (n = 157) were prospectively assessed. Patients undergoing hip and knee arthroplasty completed an OHS or OKS, respectively, preoperatively and were asked to recall their preoperative condition while completing the same score one year after surgery. Results. A mean difference of 0.04 points (95% confidence intervals (CI) -15.64 to 15.72, p = 0.97) between the actual and the recalled OHS was observed. The mean difference in the OKS was 1.59 points (95% CI -11.57 to 14.75, p = 0.10). There was excellent reliability for the ‘average measures’ intra-class correlation for both the OHS (r = 0.802) and the OKS (r = 0.772). However, this reliability was diminished for the individuals OHS (r = 0.670) and OKS (r = 0.629) using single measures intra-class correlation. Bland–Altman plots demonstrated wide variation in the individual patient’s ability to recall their preoperative score (95% CI ± 16 for OHS, 95% CI ± 13 for OKS). Conclusion. Prospective preoperative collection of OHS and OKS remains the benchmark. Using recalled scores one year following hip and knee arthroplasty is an alternative when used to assess a cohort of patients. However, the recall of an individual patient’s preoperative score should not be relied upon due to the diminished reliability and wide CI. Cite this article: T. F. M. Yeoman, N. D. Clement, D. Macdonald, M. Moran. Recall of preoperative Oxford Hip and Knee Scores one year after arthroplasty is an alternative and reliable technique when used for a cohort of patients. Bone Joint
Objectives. The aim of this study was to investigate the effect of hyperglycaemia on oxidative stress markers and inflammatory and matrix gene expression within tendons of normal and diabetic rats and to give insights into the processes involved in tendinopathy. Methods. Using tenocytes from normal Sprague-Dawley rats, cultured both in control and high glucose conditions, reactive oxygen species (ROS) production, cell proliferation, messenger RNA (mRNA) expression of NADPH oxidase (NOX) 1 and 4, interleukin-6 (IL-6), matrix metalloproteinase (MMP)-2, tissue inhibitors of matrix metalloproteinase (TIMP)-1 and -2 and type I and III collagens were determined after 48 and 72 hours in vitro. In an in vivo study, using diabetic rats and controls, NOX1 and 4 expressions in Achilles tendon were also determined. Results. In tenocyte cultures grown under high glucose conditions, gene expressions of NOX1, MMP-2, TIMP-1 and -2 after 48 and 72 hours, NOX4 after 48 hours and IL-6, type III collagen and TIMP-2 after 72 hours were significantly higher than those in control cultures grown under control glucose conditions. Type I collagen expression was significantly lower after 72 hours. ROS accumulation was significantly higher after 48 hours, and cell proliferation after 48 and 72 hours was significantly lower in high glucose than in control glucose conditions. In the diabetic rat model, NOX1 expression within the Achilles tendon was also significantly increased. Conclusion. This study suggests that high glucose conditions upregulate the expression of mRNA for NOX1 and IL-6 and the production of ROS. Moreover, high glucose conditions induce an abnormal tendon matrix expression pattern of type I collagen and a decrease in the proliferation of rat tenocytes. Cite this article: Y. Ueda, A. Inui, Y. Mifune, R. Sakata, T. Muto, Y. Harada, F. Takase, T. Kataoka, T. Kokubu, R. Kuroda. The effects of high glucose condition on rat tenocytes in vitro and rat Achilles tendon in vivo. Bone Joint
Objectives. This study aimed to assess the effect of age and osteoporosis on the proliferative and differentiating capacity of bone-marrow-derived mesenchymal stem cells (MSCs) in female rats. We also discuss the role of these factors on expression and migration of cells along the C-X-C chemokine receptor type 4 (CXCR-4) / stromal derived factor 1 (SDF-1) axis. Methods. Mesenchymal stem cells were harvested from the femora of young, adult, and osteopenic Wistar rats. Cluster of differentiation (CD) marker and CXCR-4 expression was measured using flow cytometry. Cellular proliferation was measured using Alamar Blue, osteogenic differentiation was measured using alkaline phosphatase expression and alizarin red production, and adipogenic differentiation was measured using Oil red O. Cells were incubated in Boyden chambers to quantify their migration towards SDF-1. Data was analyzed using a Student’s t-test, where p-values < 0.05 were considered significant. Results. CD marker expression and proliferation of the MSCs from the three groups was not significantly different. The young MSCs demonstrated significantly increased differentiation into bone and fat and superior migration towards SDF-1. The migration of SDF-1 doubled with young rats compared with the adult rats (p = 0.023) and it was four times higher when compared with cells isolated from ovariectomized (OVX) osteopenic rats (p = 0.013). Conclusion. Young rat MSCs are significantly more responsive to osteogenic differentiation, and, contrary to other studies, also demonstrated increased adipogenic differentiation compared with cells from adult and ostopenic rats. Young-rat-derived cells also showed superior migration towards SDF-1 compared with MSCs from OVX and adult control rats. Cite this article: A. Sanghani-Kerai, L. Osagie-Clouard, G. Blunn, M. Coathup. The influence of age and osteoporosis on bone marrow stem cells from rats. Bone Joint
Objectives. Metabolic syndrome and low-grade systemic inflammation are associated with knee osteoarthritis (OA), but the relationships between these factors and OA in other synovial joints are unclear. The aim of this study was to determine if a high-fat/high-sucrose (HFS) diet results in OA-like joint damage in the shoulders, knees, and hips of rats after induction of obesity, and to identify potential joint-specific risks for OA-like changes. Methods. A total of 16 male Sprague-Dawley rats were allocated to either the diet-induced obesity group (DIO, 40% fat, 45% sucrose, n = 9) or a chow control diet (n = 7) for 12 weeks. At sacrifice, histological assessments of the shoulder, hip, and knee joints were performed. Serum inflammatory mediators and body composition were also evaluated. The total Mankin score for each animal was assessed by adding together the individual Modified Mankin scores across all three joints. Linear regression modelling was conducted to evaluate predictive relationships between serum mediators and total joint damage. Results. The HFS diet, in the absence of trauma, resulted in increased joint damage in the shoulder and knee joints of rats. Hip joint damage, however, was not significantly affected by DIO, consistent with findings in human studies. The total Mankin score was increased in DIO animals compared with the chow group, and was associated with percentage of body fat. Positive significant predictive relationships for total Mankin score were found between body fat and two serum mediators (interleukin 1 alpha (IL-1α) and vascular endothelial growth factor (VEGF)). Conclusion. Systemic inflammatory alterations from DIO in this model system may result in a higher risk for development of knee, shoulder, and multi-joint damage with a HFS diet. Cite this article: K. H. Collins, D. A. Hart, R. A. Seerattan, R. A. Reimer, W. Herzog. High-fat/high-sucrose diet-induced obesity results in joint-specific development of osteoarthritis-like degeneration in a rat model. Bone Joint
Objectives. The aim of this study was to identify key pathological genes in osteoarthritis (OA). Methods. We searched and downloaded mRNA expression data from the Gene Expression Omnibus database to identify differentially expressed genes (DEGs) of joint synovial tissues from OA and normal individuals. Gene Ontology (GO) and Kyoto Encyclopaedia of Genes and Genomes (KEGG) pathway analyses were used to assess the function of identified DEGs. The protein-protein interaction (PPI) network and transcriptional factors (TFs) regulatory network were used to further explore the function of identified DEGs. The quantitative real-time polymerase chain reaction (qRT-PCR) was applied to validate the result of bioinformatics analysis. Electronic validation was performed to verify the expression of selected DEGs. The diagnosis value of identified DEGs was accessed by receiver operating characteristic (ROC) analysis. Results. A total of 1085 DEGs were identified. KEGG pathway analysis displayed that Wnt was a significantly enriched signalling pathway. Some hub genes with high interactions such as USP46, CPVL, FKBP5, FOSL2, GADD45B, PTGS1, and ZNF423 were identified in the PPI and TFs network. The results of qRT-PCR showed that GADD45B, ADAMTS1, and TFAM were down-regulated in joint synovial tissues of OA, which was consistent with the bioinformatics analysis. The expression levels of USP46, CPVL, FOSL2, and PTGS1 in electronic validation were compatible with the bio-informatics result. CPVL and TFAM had a potential diagnostic value for OA based on the ROC analysis. Conclusion. The deregulated genes including USP46, CPVL, FKBP5, FOSL2, GADD45B, PTGS1, ZNF423, ADAMTS1, and TFAM might be involved in the pathology of OA. Cite this article: X. Zhang, Y. Bu, B. Zhu, Q. Zhao, Z. Lv, B. Li, J. Liu. Global transcriptome analysis to identify critical genes involved in the pathology of osteoarthritis. Bone Joint
Objectives. The aims of this study were to determine whether the administration of anti-inflammatory and antifibrotic agents affect the proliferation, viability, and expression of markers involved in the fibrotic development of the fibroblasts obtained from arthrofibrotic tissue in vitro, and to evaluate the effect of the agents on arthrofibrosis prevention in vivo. Methods. Dexamethasone, diclofenac, and decorin, in different concentrations, were employed to treat fibroblasts from arthrofibrotic tissue (AFib). Cell proliferation was measured by DNA quantitation, and viability was analyzed by Live/Dead staining. The levels of procollagen type I N-terminal propeptide (PINP) and procollagen type III N-terminal propeptide (PIIINP) were evaluated with enzyme-linked immunosorbent assay (ELISA) kits. In addition, the expressions of fibrotic markers were detected by real-time polymerase chain reaction (PCR). Fibroblasts isolated from healthy tissue (Fib) served as control. Further, a rabbit model of joint contracture was used to evaluate the antifibrotic effect of the three different agents. Results. Dexamethasone maintained the viability and promoted the proliferation of AFib. Diclofenac decreased the viability and inhibited the cell proliferation during the first week of cultivation. However, decorin inhibited AFib proliferation and downregulated the expressions of fibrotic markers. Additionally, decorin could improve the flexion contracture angle and inhibit the deposition of interstitial matrix components in the rabbit joint model. Conclusion. Decorin decreased the expression of myofibroblast markers in AFib, inhibited the proliferation of AFib, and prevented the initial procedure of arthrofibrosis in vivo, suggesting that decorin could be a promising treatment to inhibit the development of arthrofibrosis. Cite this article: X. Tang, S. Teng, M. Petri, C. Krettek, C. Liu, M. Jagodzinski. The effect of anti-inflammatory and antifibrotic agents on fibroblasts obtained from arthrofibrotic tissue: An in vitro and in vivo study. Bone Joint
Objectives. Malalignment of the tibial component could influence the long-term survival of a total knee arthroplasty (TKA). The object of this study was to investigate the biomechanical effect of varus and valgus malalignment on the tibial component under stance-phase gait cycle loading conditions. Methods. Validated finite element models for varus and valgus malalignment by 3° and 5° were developed to evaluate the effect of malalignment on the tibial component in TKA. Maximum contact stress and contact area on a polyethylene insert, maximum contact stress on patellar button and the collateral ligament force were investigated. Results. There was greater total contact stress in the varus alignment than in the valgus, with more marked difference on the medial side. An increase in ligament force was clearly demonstrated, especially in the valgus alignment and force exerted on the medial collateral ligament also increased. Conclusion. These results highlight the importance of accurate surgical reconstruction of the coronal tibial alignment of the knee joint. Varus and valgus alignments will influence wear and ligament stability, respectively in TKA. Cite this article: D-S. Suh, K-T. Kang, J. Son, O-R. Kwon, C. Baek, Y-G. Koh. Computational study on the effect of malalignment of the tibial component on the biomechanics of total knee arthroplasty: A Finite Element Analysis. Bone Joint
Objectives. Recently, high failure rates of metal-on-metal (MOM) hip implants have raised concerns of cobalt toxicity. Adverse reactions occur to cobalt nanoparticles (CoNPs) and cobalt ions (Co. 2+. ) during wear of MOM hip implants, but the toxic mechanism is not clear. Methods. To evaluate the protective effect of zinc ions (Zn. 2+. ), Balb/3T3 mouse fibroblast cells were pretreated with 50 μM Zn. 2+. for four hours. The cells were then exposed to different concentrations of CoNPs and Co. 2+. for four hours, 24 hours and 48 hours. The cell viabilities, reactive oxygen species (ROS) levels, and inflammatory cytokines were measured. Results. CoNPs and Co. 2+. can induce the increase of ROS and inflammatory cytokines, such as tumour necrosis factor α (TNF-α), interleukin-1β (IL-1β) and interleukin-6 (IL-6). However, Zn pretreatment can significantly prevent cytotoxicity induced by CoNPs and Co. 2+. , decrease ROS production, and decrease levels of inflammatory cytokines in Balb/3T3 mouse fibroblast cells. Conclusion. These results suggest that Zn pretreatment can provide protection against inflammation and cytotoxicity induced by CoNPs and Co. 2+. in Balb/3T3 cells. Cite this article: Y. Liu, H. Zhu, H. Hong, W. Wang, F. Liu. Can zinc protect cells from the cytotoxic effects of cobalt ions and nanoparticles derived from metal-on-metal joint arthroplasties? Bone Joint
Objectives. This study investigates the reporting of health-related quality of life (HRQoL) in patients following hip fracture. We compare the relative merits and make recommendations for the use for two methods of measuring HRQoL; (i) including patients who died during follow-up and (ii) including survivors only. Methods. The World Hip Trauma Evaluation has previously reported changes in HRQoL using EuroQol-5D for patients with hip fractures. We performed additional analysis to investigate the effect of including or excluding those patients who died during the first four months of the follow-up period. Results. The dataset included 503 patients, 25 of whom died between 30 days and four months of injury. There was a statistically significant difference in 30-day HRQoL between those alive (mean 0.331 and standard deviation (. sd. ) 0.360) and those dead (mean 0.156 and . sd. 0.421) by four months (independent-samples t-test; p 0.022). The estimated difference of 0.175 in HRQoL (95% confidence interval 0.025 to 0.325) was also highly clinically significant. Conclusion. When reporting HRQoL for patients after a hip fracture, excluding patients who die during follow-up leads to an overestimate of the effects of the intervention or treatment pathway. We would recommend that death-adjusted estimates should be used routinely when reporting HRQoL in this population. Cite this article: N. Parsons, X. L. Griffin, J. Achten, T. J. Chesser, S. E. Lamb, M. L. Costa. Modelling and estimation of health-related quality of life after hip fracture: A re-analysis of data from a prospective cohort study. Bone Joint
Objectives. In order to address acetabular defects, porous metal revision acetabular components and augments have been developed, which require fixation to each other. The fixation technique that results in the smallest relative movement between the components, as well as its influence on the primary stability with the host bone, have not previously been determined. Methods. A total of 18 composite hemipelvises with a Paprosky IIB defect were implanted using a porous titanium 56 mm multihole acetabular component and 1 cm augment. Each acetabular component and augment was affixed to the bone using two screws, while the method of fixation between the acetabular component and augment varied for the three groups of six hemipelvises: group S, screw fixation only; group SC, screw plus cement fixation; group C, cement fixation only. The implanted hemipelvises were cyclically loaded to three different loading maxima (0.5 kN, 0.9 kN, and 1.8 kN). Results. Screw fixation alone resulted in up to three times more movement (p = 0.006), especially when load was increased to 100% (p < 0.001), than with the other two fixation methods (C and SC). No significant difference was noted when a screw was added to the cement fixation. Increased load resulted in increased relative movement between the interfaces in all fixation methods (p < 0.001). Conclusion. Cement fixation between a porous titanium acetabular component and augment is associated with less relative movement than screw fixation alone for all implant interfaces, particularly with increasing loads. Adding a screw to the cement fixation did not offer any significant advantage. These results also show that the stability of the tested acetabular component/augment interface affects the stability of the construct that is affixed to the bone. Cite this article: N. A. Beckmann, R. G. Bitsch, M. Gondan, M. Schonhoff, S. Jaeger. Comparison of the stability of three fixation techniques between porous metal acetabular components and augments. Bone Joint
Objectives. This study aimed to examine the effects of SRT1720, a potent SIRT1 activator, on osteoarthritis (OA) progression using an experimental OA model. Methods. Osteoarthritis was surgically induced by destabilization of the medial meniscus in eight-week-old C57BL/6 male mice. SRT1720 was administered intraperitoneally twice a week after surgery. Osteoarthritis progression was evaluated histologically using the Osteoarthritis Research Society International (OARSI) score at four, eight, 12 and 16 weeks. The expression of SIRT1, matrix metalloproteinase 13 (MMP-13), a disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5), cleaved caspase-3, PARP p85, and acetylated nuclear factor (NF)-κB p65 in cartilage was examined by immunohistochemistry. Synovitis was also evaluated histologically. Primary mouse epiphyseal chondrocytes were treated with SRT1720 in the presence or absence of interleukin 1 beta (IL-1β), and gene expression changes were examined by real-time polymerase chain reaction (PCR). Results. The OARSI score was significantly lower in mice treated with SRT1720 than in control mice at eight and 12 weeks associated with the decreased size of osteophytes at four and eight weeks. The delayed OA progression in the mice treated with SRT1720 was also associated with increased SIRT1-positive chondrocytes and decreased MMP-13-, ADAMTS-5-, cleaved caspase-3-, PARP p85-, and acetylated NF-κB p65-positive chondrocytes and decreased synovitis at four and eight weeks. SRT1720 treatment partially rescued the decreases in collagen type II alpha 1 (COL2A1) and aggrecan caused by IL-1β, while also reducing the induction of MMP-13 by IL-1β in vitro. Conclusion. The intraperitoneal injection of SRT1720 attenuated experimental OA progression in mice, indicating that SRT1720 could be a new therapeutic approach for OA. Cite this article: K. Nishida, T. Matsushita, K. Takayama, T. Tanaka, N. Miyaji, K. Ibaraki, D. Araki, N. Kanzaki, T. Matsumoto, R. Kuroda. Intraperitoneal injection of the SIRT1 activator SRT1720 attenuates the progression of experimental osteoarthritis in mice. Bone Joint
Objectives. Little is known about tissue changes underlying bone marrow lesions (BMLs) in non-weight-bearing joints with osteoarthritis (OA). Our aim was to characterize BMLs in OA of the hand using dynamic histomorphometry. We therefore quantified bone turnover and angiogenesis in subchondral bone at the base of the thumb, and compared the findings with control bone from hip OA. Methods. Patients with OA at the base of the thumb, or the hip, underwent preoperative MRI to assess BMLs, and tetracycline labelling to determine bone turnover. Three groups were compared: trapezium bones removed by trapeziectomy from patients with thumb base OA (n = 20); femoral heads with (n = 24); and those without (n = 9) BMLs obtained from patients with hip OA who underwent total hip arthroplasty. Results. All trapezium bones demonstrated MRI-defined BMLs. Compared with femoral heads without BMLs, the trapezia demonstrated significantly higher bone turnover (mean . sd. 0.2 (0.1) versus 0.01 (0.01) µm. 3. /µm. 2. /day), mineralizing surface (18.5% (13.1) versus 1.4% (1.3)) and vascularity (5.2% (1.1) versus 1.2% (0.6)). Femoral heads with BMLs exhibited higher bone turnover (0.3 (0.2) versus 0.2 (0.1) µm. 3. /µm. 2. /day), a higher mineralization rate (26.6% (10.6) versus 18.6% (11.9)) and greater trabecular thickness (301.3 µm (108) versus 163.6 µm (24.8)) than the trapezia. Conclusion. Bone turnover and angiogenesis were enhanced in BMLs of both the thumb base and hip OA, of which the latter exhibited the highest bone turnover. Thus, the increase in bone turnover in weight-bearing joints like the hip may be more pronounced than less mechanically loaded osteoarthritic joints demonstrating BMLs. The histological changes observed may explain the water signal from BMLs on MRI. Cite this article: M. Shabestari, N. J. Kise, M. A. Landin, S. Sesseng, J. C. Hellund, J. E. Reseland, E. F. Eriksen, I. K. Haugen. Enhanced angiogenesis and increased bone turnover characterize bone marrow lesions in osteoarthritis at the base of the thumb. Bone Joint
