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Bone & Joint Research
Vol. 13, Issue 4 | Pages 193 - 200
23 Apr 2024
Reynolds A Doyle R Boughton O Cobb J Muirhead-Allwood S Jeffers J

Aims

Manual impaction, with a mallet and introducer, remains the standard method of installing cementless acetabular cups during total hip arthroplasty (THA). This study aims to quantify the accuracy and precision of manual impaction strikes during the seating of an acetabular component. This understanding aims to help improve impaction surgical techniques and inform the development of future technologies.

Methods

Posterior approach THAs were carried out on three cadavers by an expert orthopaedic surgeon. An instrumented mallet and introducer were used to insert cementless acetabular cups. The motion of the mallet, relative to the introducer, was analyzed for a total of 110 strikes split into low-, medium-, and high-effort strikes. Three parameters were extracted from these data: strike vector, strike offset, and mallet face alignment.


Bone & Joint Research
Vol. 11, Issue 2 | Pages 134 - 142
23 Feb 2022
Luo P Cheng S Zhang F Feng R Xu K Jing W Xu P

Aims

The aim of this study was to explore the genetic correlation and causal relationship between blood plasma proteins and rheumatoid arthritis (RA).

Methods

Based on the genome-wide association studies (GWAS) summary statistics of RA from European descent and the GWAS summary datasets of 3,622 plasma proteins, we explored the relationship between RA and plasma proteins from three aspects. First, linkage disequilibrium score regression (LD score regression) was applied to detect the genetic correlation between RA and plasma proteins. Mendelian randomization (MR) analysis was then used to evaluate the causal association between RA and plasma proteins. Finally, GEO2R was used to screen the differentially expressed genes (DEGs) between patients with RA and healthy controls.


Bone & Joint Research
Vol. 5, Issue 11 | Pages 538 - 543
1 Nov 2016
Weeks BK Hirsch R Nogueira RC Beck BR

Objectives. The aim of the current study was to assess whether calcaneal broadband ultrasound attenuation (BUA) can predict whole body and regional dual-energy x-ray absorptiometry (DXA)-derived bone mass in healthy, Australian children and adolescents at different stages of maturity. Methods. A total of 389 boys and girls across a wide age range (four to 18 years) volunteered to participate. The estimated age of peak height velocity (APHV) was used to classify children into pre-, peri-, and post-APHV groups. BUA was measured at the non-dominant heel with quantitative ultrasonometry (QUS) (Lunar Achilles Insight, GE), while bone mineral density (BMD) and bone mineral content (BMC) were examined at the femoral neck, lumbar spine and whole body (DXA, XR-800, Norland). Associations between BUA and DXA-derived measures were examined with Pearson correlations and linear regression. Participants were additionally ranked in quartiles for QUS and DXA measures in order to determine agreement in rankings. Results. For the whole sample, BUA predicted 29% of the study population variance in whole body BMC and BMD, 23% to 24% of the study population variance in lumbar spine BMC and BMD, and 21% to 24% of the variance in femoral neck BMC and BMD (p < 0.001). BUA predictions were strongest for the most mature participants (pre-APHV R. 2. = 0.03 to 0.19; peri-APHV R. 2. = 0.05 to 0.17; post-APHV R. 2. = 0.18 to 0.28) and marginally stronger for girls (R. 2. = 0.25-0.32, p < 0.001) than for boys (R. 2. = 0.21-0.27, p < 0.001). Agreement in quartile rankings between QUS and DXA measures of bone mass was generally poor (27.3% to 38.2%). Conclusion. Calcaneal BUA has a weak to moderate relationship with DXA measurements of bone mass in children, and has a tendency to misclassify children on the basis of quartile rankings. Cite this article: B. K. Weeks, R. Hirsch, R. C. Nogueira, B. R. Beck. Is calcaneal broadband ultrasound attenuation a valid index of dual-energy x-ray absorptiometry-derived bone mass in children? Bone Joint Res 2016;5:538–543. DOI: 10.1302/2046-3758.511.BJR-2016-0116.R1


Bone & Joint Research
Vol. 10, Issue 1 | Pages 1 - 9
1 Jan 2021
Garner A Dandridge O Amis AA Cobb JP van Arkel RJ

Aims. Unicompartmental knee arthroplasty (UKA) and bicompartmental knee arthroplasty (BCA) have been associated with improved functional outcomes compared to total knee arthroplasty (TKA) in suitable patients, although the reason is poorly understood. The aim of this study was to measure how the different arthroplasties affect knee extensor function. Methods. Extensor function was measured for 16 cadaveric knees and then retested following the different arthroplasties. Eight knees underwent medial UKA then BCA, then posterior-cruciate retaining TKA, and eight underwent the lateral equivalents then TKA. Extensor efficiency was calculated for ranges of knee flexion associated with common activities of daily living. Data were analyzed with repeated measures analysis of variance (α = 0.05). Results. Compared to native, there were no reductions in either extension moment or efficiency following UKA. Conversion to BCA resulted in a small decrease in extension moment between 70° and 90° flexion (p < 0.05), but when examined in the context of daily activity ranges of flexion, extensor efficiency was largely unaffected. Following TKA, large decreases in extension moment were measured at low knee flexion angles (p < 0.05), resulting in 12% to 43% reductions in extensor efficiency for the daily activity ranges. Conclusion. This cadaveric study found that TKA resulted in inferior extensor function compared to UKA and BCA. This may, in part, help explain the reported differences in function and satisfaction differences between partial and total knee arthroplasty. Cite this article: Bone Joint Res 2021;10(1):1–9


Bone & Joint Research
Vol. 9, Issue 10 | Pages 653 - 666
7 Oct 2020
Li W Li G Chen W Cong L

Aims. The aim of this study was to systematically compare the safety and accuracy of robot-assisted (RA) technique with conventional freehand with/without fluoroscopy-assisted (CT) pedicle screw insertion for spine disease. Methods. A systematic search was performed on PubMed, EMBASE, the Cochrane Library, MEDLINE, China National Knowledge Infrastructure (CNKI), and WANFANG for randomized controlled trials (RCTs) that investigated the safety and accuracy of RA compared with conventional freehand with/without fluoroscopy-assisted pedicle screw insertion for spine disease from 2012 to 2019. This meta-analysis used Mantel-Haenszel or inverse variance method with mixed-effects model for heterogeneity, calculating the odds ratio (OR), mean difference (MD), standardized mean difference (SMD), and 95% confidence intervals (CIs). The results of heterogeneity, subgroup analysis, and risk of bias were analyzed. Results. Ten RCTs with 713 patients and 3,331 pedicle screws were included. Compared with CT, the accuracy rate of RA was superior in Grade A with statistical significance and Grade A + B without statistical significance. Compared with CT, the operating time of RA was longer. The difference between RA and CT was statistically significant in radiation dose. Proximal facet joint violation occurred less in RA than in CT. The postoperative Oswestry Disability Index (ODI) of RA was smaller than that of CT, and there were some interesting outcomes in our subgroup analysis. Conclusion. RA technique could be viewed as an accurate and safe pedicle screw implantation method compared to CT. A robotic system equipped with optical intraoperative navigation is superior to CT in accuracy. RA pedicle screw insertion can improve accuracy and maintain stability for some challenging areas. Cite this article: Bone Joint Res 2020;9(10):653–666


Bone & Joint Research
Vol. 9, Issue 8 | Pages 468 - 476
1 Aug 2020
Parsons NR Costa ML Achten J Griffin XL

Aims. To assess the variation in pre-fracture quality of life (QoL) within the UK hip fracture population, and quantify the nature and strength of associations between QoL and other routinely collected patient characteristics and treatment choices. Methods. The World Hip Trauma Evaluation (WHiTE) study, an observational cohort study of UK hip fracture patients, collects a range of routine data and a health-related QoL score (EuroQol five-dimension questionnaire (EQ-5D)). Pre-fracture QoL data are summarized and statistical models fitted to understand associations between QoL, patient characteristics, fracture types, and operations. Results. Fitting a multiple linear regression model indicated that 36.5% of the variance in pre-fracture EQ-5D scores was explained by routinely collected patient characteristics: sex (0.14%), age (0.17%), American Society of Anesthesiologists (ASA) score (0.73%), Abbreviated Mental Test Score (AMTS; 1.3%), pre-fracture mobility (11.2%), and EQ-5D respondent (participant, relative, or carer; 23.0%). There was considerable variation in pre-fracture EQ-5D scores between operations within fracture types. Participants with trochanteric fractures reported statistically significant but not clinically relevant lower pre-fracture QoL than those with intracapsular fractures. Participants with intracapsular fractures treated with internal fixation or total hip arthroplasty (THA) reported better QoL than those treated with hemiarthroplasty with the overall fittest group receiving THA. Conclusion. Pre-fracture QoL varies considerably between hip fracture patients; it is generally higher in younger than older patients, patients with better mobility, and those patients who live more independently. Pre-fracture QoL is significantly associated with a range of patient characteristics (e.g. age, mobility, residency). These data explain ~35% of the variation in QoL. Cite this article: Bone Joint Res 2020;9(8):468–476


Bone & Joint Research
Vol. 9, Issue 7 | Pages 429 - 439
1 Jul 2020
Tahir M Chaudhry EA Zaffar Z Anwar K Mamoon MAH Ahmad M Jamali AR Mehboob G

Aims. We hypothesized that the wide-awake local anaesthesia with no tourniquet (WALANT) technique is cost-effective, easy to use, safe, and reproducible, with a low learning curve towards mastery, having a high patient satisfaction rate. Furthermore, WALANT would be a suitable alternative for the austere and developing nation environments where lack of funds and resources are a common issue. Methods. This was a randomized control trial of 169 patients who required surgery for closed isolated distal radius fractures. The study was performed between March 2016 and April 2019 at a public sector level 1 trauma centre. General anaesthesia was used in 56 patients, Bier’s block in 58 patients, and WALANT in 55 patients. Data were collected on pre-, peri-, and postoperative parameters, clinical outcome, hospital costs, and patient satisfaction. One-way analysis of variance (ANOVA) was used with a p-value of 0.05 being significant. Results. Operations with WALANT proceeded sooner, and patients recovered faster, resulting in mean fewer missed working days (7.8 (SD 1.67)) compared with general anaesthesia (20.1 (SD 7.37)) or Bier’s block (14.1 (SD 7.65)) (p < 0.001). The WALANT patients did not develop complications, while the other patients did (p < 0.04). Clinical outcomes did not differ, nor did surgeon qualification affect clinical outcomes. Mean hospital costs were lower for WALANT ($428.50 (SD 77.71)) than for general anaesthesia ($630.63 (SD 114.77)) or Bier’s block ($734.00 (SD 37.54)) (p < 0.001). Patient satisfaction was also higher (p < 0.001). Conclusion. WALANT for distal radius fractures results in a faster recovery, is more cost-effective, has similar clinical outcomes, and has fewer complications than general anaesthesia or Bier's block. This makes WALANT an attractive technique in any setting, but especially in middle- and low-income countries. Cite this article: Bone Joint Res 2020;9(7):429–439


Bone & Joint Research
Vol. 8, Issue 6 | Pages 246 - 252
1 Jun 2019
Liddle A Webb M Clement N Green S Liddle J German M Holland J

Objectives. Previous studies have evidenced cement-in-cement techniques as reliable in revision arthroplasty. Commonly, the original cement mantle is reshaped, aiding accurate placement of the new stem. Ultrasonic devices selectively remove cement, preserve host bone, and have lower cortical perforation rates than other techniques. As far as the authors are aware, the impact of ultrasonic devices on final cement-in-cement bonds has not been investigated. This study assessed the impact of cement removal using the Orthosonics System for Cemented Arthroplasty Revision (OSCAR; Orthosonics) on final cement-in-cement bonds. Methods. A total of 24 specimens were manufactured by pouring cement (Simplex P Bone Cement; Stryker) into stainless steel moulds, with a central rod polished to Stryker Exeter V40 specifications. After cement curing, the rods were removed and eight specimens were allocated to each of three internal surface preparation groups: 1) burr; 2) OSCAR; and 3) no treatment. Internal holes were recemented, and each specimen was cut into 5 mm discs. Shear testing of discs was completed by a technician blinded to the original grouping, recording ultimate shear strengths. Scanning electron microscopy (SEM) was completed, inspecting surfaces of shear-tested specimens. Results. The mean shear strength for OSCAR-prepared specimens (33.6 MPa) was significantly lower than for the control (46.3 MPa) and burr (45.8 MPa) groups (p < 0.001; one-way analysis of variance (ANOVA) with Tukey’s post hoc analysis). There was no significant difference in shear strengths between control and burr groups (p = 0.57). Scanning electron microscopy of OSCAR specimens revealed evidence of porosity undiscovered in previous studies. Conclusion. Results show that the cement removal technique impacts on final cement-in-cement bonds. This in vitro study demonstrates significantly weaker bonds when using OSCAR prior to recementation into an old cement mantle compared with cement prepared with a burr or no treatment. This infers that care must be taken in surgical decision-making regarding cement removal techniques used during cement-in-cement revision arthroplasty, suggesting that the risks and benefits of ultrasonic cement removal need consideration. Cite this article: A. Liddle, M. Webb, N. Clement, S. Green, J. Liddle, M. German, J. Holland. Ultrasonic cement removal in cement-in-cement revision total hip arthroplasty: What is the effect on the final cement-in-cement bond? Bone Joint Res 2019;8:246–252. DOI: 10.1302/2046-3758.86.BJR-2018-0313.R1


Bone & Joint Research
Vol. 8, Issue 1 | Pages 3 - 10
1 Jan 2019
Hernandez P Sager B Fa A Liang T Lozano C Khazzam M

Objectives. The purpose of this study was to examine the bactericidal efficacy of hydrogen peroxide (H. 2. O. 2. ) on Cutibacterium acnes (C. acnes). We hypothesize that H. 2. O. 2. reduces the bacterial burden of C. acnes. Methods. The effect of H. 2. O. 2. was assessed by testing bactericidal effect, time course analysis, growth inhibition, and minimum bactericidal concentration. To assess the bactericidal effect, bacteria were treated for 30 minutes with 0%, 1%, 3%, 4%, 6%, 8%, or 10% H. 2. O. 2. in saline or water and compared with 3% topical H. 2. O. 2. solution. For time course analysis, bacteria were treated with water or saline (controls), 3% H. 2. O. 2. in water, 3% H. 2. O. 2. in saline, or 3% topical solution for 5, 10, 15, 20, and 30 minutes. Results were analyzed with a two-way analysis of variance (ANOVA) (p < 0.05). Results. Minimum inhibitory concentration of H. 2. O. 2. after 30 minutes is 1% for H. 2. O. 2. prepared in saline and water. The 3% topical solution was as effective when compared with the 1% H. 2. O. 2. prepared in saline or water. The controls of both saline and water showed no reduction of bacteria. After five minutes of exposure, all mixtures of H. 2. O. 2. reduced the percentage of live bacteria, with the topical solution being most effective (p < 0.0001). Maximum growth inhibition was achieved with topical 3% H. 2. O. 2. . Conclusion. The inexpensive and commercially available topical solution of 3% H. 2. O. 2. demonstrated superior bactericidal effect as observed in the minimum bactericidal inhibitory concentration, time course, and colony-forming unit (CFU) inhibition assays. These results support the use of topical 3% H. 2. O. 2. for five minutes before surgical skin preparation prior to shoulder surgery to achieve eradication of C. acnes for the skin. Cite this article: P. Hernandez, B. Sager, A. Fa, T. Liang, C. Lozano, M. Khazzam. Bactericidal efficacy of hydrogen peroxide on Cutibacterium acnes. Bone Joint Res 2019;8:3–10. DOI: 10.1302/2046-3758.81.BJR-2018-0145.R1


Aims

This study intended to investigate the effect of vericiguat (VIT) on titanium rod osseointegration in aged rats with iron overload, and also explore the role of VIT in osteoblast and osteoclast differentiation.

Methods

In this study, 60 rats were included in a titanium rod implantation model and underwent subsequent guanylate cyclase treatment. Imaging, histology, and biomechanics were used to evaluate the osseointegration of rats in each group. First, the impact of VIT on bone integration in aged rats with iron overload was investigated. Subsequently, VIT was employed to modulate the differentiation of MC3T3-E1 cells and RAW264.7 cells under conditions of iron overload.


Bone & Joint Research
Vol. 13, Issue 1 | Pages 4 - 18
2 Jan 2024
Wang Y Wu Z Yan G Li S Zhang Y Li G Wu C

Aims

cAMP response element binding protein (CREB1) is involved in the progression of osteoarthritis (OA). However, available findings about the role of CREB1 in OA are inconsistent. 666-15 is a potent and selective CREB1 inhibitor, but its role in OA is unclear. This study aimed to investigate the precise role of CREB1 in OA, and whether 666-15 exerts an anti-OA effect.

Methods

CREB1 activity and expression of a disintegrin and metalloproteinase with thrombospondin motifs 4 (ADAMTS4) in cells and tissues were measured by immunoblotting and immunohistochemical (IHC) staining. The effect of 666-15 on chondrocyte viability and apoptosis was examined by cell counting kit-8 (CCK-8) assay, JC-10, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labelling (TUNEL) staining. The effect of 666-15 on the microstructure of subchondral bone, and the synthesis and catabolism of cartilage, in anterior cruciate ligament transection mice were detected by micro-CT, safranin O and fast green (S/F), immunohistochemical staining, and enzyme-linked immunosorbent assay (ELISA).


Bone & Joint Research
Vol. 12, Issue 12 | Pages 734 - 746
12 Dec 2023
Chen M Hu C Hsu Y Lin Y Chen K Ueng SWN Chang Y

Aims

Therapeutic agents that prevent chondrocyte loss, extracellular matrix (ECM) degradation, and osteoarthritis (OA) progression are required. The expression level of epidermal growth factor (EGF)-like repeats and discoidin I-like domains-containing protein 3 (EDIL3) in damaged human cartilage is significantly higher than in undamaged cartilage. However, the effect of EDIL3 on cartilage is still unknown.

Methods

We used human cartilage plugs (ex vivo) and mice with spontaneous OA (in vivo) to explore whether EDIL3 has a chondroprotective effect by altering OA-related indicators.


Bone & Joint Research
Vol. 12, Issue 1 | Pages 33 - 45
16 Jan 2023
Li B Ding T Chen H Li C Chen B Xu X Huang P Hu F Guo L

Aims

Circular RNA (circRNA) is involved in the regulation of articular cartilage degeneration induced by inflammatory factors or oxidative stress. In a previous study, we found that the expression of circStrn3 was significantly reduced in chondrocytes of osteoarthritis (OA) patients and OA mice. Therefore, the aim of this paper was to explore the role and mechanism of circStrn3 in osteoarthritis.

Methods

Minus RNA sequencing, fluorescence in situ hybridization, and quantitative real-time polymerase chain reaction (qRT-PCR) were used to detect the expression of circStrn3 in human and mouse OA cartilage tissues and chondrocytes. Chondrocytes were then stimulated to secrete exosomal miR-9-5p by cyclic tensile strain. Intra-articular injection of exosomal miR-9-5p into the model induced by destabilized medial meniscus (DMM) surgery was conducted to alleviate OA progression.


Bone & Joint Research
Vol. 13, Issue 2 | Pages 52 - 65
1 Feb 2024
Yao C Sun J Luo W Chen H Chen T Chen C Zhang B Zhang Y

Aims

To investigate the effects of senescent osteocytes on bone homeostasis in the progress of age-related osteoporosis and explore the underlying mechanism.

Methods

In a series of in vitro experiments, we used tert-Butyl hydroperoxide (TBHP) to induce senescence of MLO-Y4 cells successfully, and collected conditioned medium (CM) and senescent MLO-Y4 cell-derived exosomes, which were then applied to MC3T3-E1 cells, separately, to evaluate their effects on osteogenic differentiation. Furthermore, we identified differentially expressed microRNAs (miRNAs) between exosomes from senescent and normal MLO-Y4 cells by high-throughput RNA sequencing. Based on the key miRNAs that were discovered, the underlying mechanism by which senescent osteocytes regulate osteogenic differentiation was explored. Lastly, in the in vivo experiments, the effects of senescent MLO-Y4 cell-derived exosomes on age-related bone loss were evaluated in male SAMP6 mice, which excluded the effects of oestrogen, and the underlying mechanism was confirmed.


Bone & Joint Research
Vol. 12, Issue 6 | Pages 375 - 386
12 Jun 2023
Li Z

Aims

Long non-coding RNAs (lncRNAs) act as crucial regulators in osteoporosis (OP). Nonetheless, the effects and potential molecular mechanism of lncRNA PCBP1 Antisense RNA 1 (PCBP1-AS1) on OP remain largely unclear. The aim of this study was to explore the role of lncRNA PCBP1-AS1 in the pathogenesis of OP.

Methods

Using quantitative real-time polymerase chain reaction (qRT-PCR), osteogenesis-related genes (alkaline phosphatase (ALP), osteocalcin (OCN), osteopontin (OPN), and Runt-related transcription factor 2 (RUNX2)), PCBP1-AS1, microRNA (miR)-126-5p, group I Pak family member p21-activated kinase 2 (PAK2), and their relative expression levels were determined. Western blotting was used to examine the expression of PAK2 protein. Cell Counting Kit-8 (CCK-8) assay was used to measure cell proliferation. To examine the osteogenic differentiation, Alizarin red along with ALP staining was used. RNA immunoprecipitation assay and bioinformatics analysis, as well as a dual-luciferase reporter, were used to study the association between PCBP1-AS1, PAK2, and miR-126-5p.


Bone & Joint Research
Vol. 12, Issue 3 | Pages 219 - 230
10 Mar 2023
Wang L Li S Xiao H Zhang T Liu Y Hu J Xu D Lu H

Aims

It has been established that mechanical stimulation benefits tendon-bone (T-B) healing, and macrophage phenotype can be regulated by mechanical cues; moreover, the interaction between macrophages and mesenchymal stem cells (MSCs) plays a fundamental role in tissue repair. This study aimed to investigate the role of macrophage-mediated MSC chondrogenesis in load-induced T-B healing in depth.

Methods

C57BL/6 mice rotator cuff (RC) repair model was established to explore the effects of mechanical stimulation on macrophage polarization, transforming growth factor (TGF)-β1 generation, and MSC chondrogenesis within T-B enthesis by immunofluorescence and enzyme-linked immunosorbent assay (ELISA). Macrophage depletion was performed by clodronate liposomes, and T-B healing quality was evaluated by histology and biomechanics. In vitro, bone marrow-derived macrophages (BMDMs) were stretched with CELLOAD-300 load system and macrophage polarization was identified by flow cytometry and quantitative real-time polymerase chain reaction (qRT-PCR). MSC chondrogenic differentiation was measured by histochemical analysis and qRT-PCR. ELISA and qRT-PCR were performed to screen the candidate molecules that mediated the pro-chondrogenic function of mechanical stimulated BMDMs.


Aims

This study examined whether systemic administration of melatonin would have different effects on osseointegration in ovariectomized (OVX) rats, depending on whether this was administered during the day or night.

Methods

In this study, a titanium rod was implanted in the medullary cavity of one femoral metaphysis in OVX rats, and then the rats were randomly divided into four groups: Sham group (Sham, n = 10), OVX rat group (OVX, n = 10), melatonin day treatment group (OVX + MD, n = 10), and melatonin night treatment group (OVX + MN, n = 10). The OVX + MD and OVX + MN rats were treated with 30 mg/kg/day melatonin at 9 am and 9 pm, respectively, for 12 weeks. At the end of the research, the rats were killed to obtain bilateral femora and blood samples for evaluation.


Bone & Joint Research
Vol. 12, Issue 11 | Pages 677 - 690
1 Nov 2023
Wang X Jiang W Pan K Tao L Zhu Y

Aims

Currently, the effect of drug treatment for osteoporosis is relatively poor, and the side effects are numerous and serious. Melatonin is a potential drug to improve bone mass in postmenopausal women. Unfortunately, the mechanism by which melatonin improves bone metabolism remains unclear. The aim of this study was to further investigate the potential mechanism of melatonin in the treatment of osteoporosis.

Methods

The effects of melatonin on mitochondrial apoptosis protein, bmal1 gene, and related pathway proteins of RAW264.7 (mouse mononuclear macrophage leukaemia cells) were analyzed by western blot. Cell Counting Kit-8 was used to evaluate the effect of melatonin on cell viability. Flow cytometry was used to evaluate the effect of melatonin on the apoptosis of RAW264.7 cells and mitochondrial membrane potential. A reactive oxygen species (ROS) detection kit was used to evaluate the level of ROS in osteoclast precursors. We used bmal1-small interfering RNAs (siRNAs) to downregulate the Bmal1 gene. We established a postmenopausal mouse model and verified the effect of melatonin on the bone mass of postmenopausal osteoporosis in mice via micro-CT. Bmal1 lentiviral activation particles were used to establish an in vitro model of overexpression of the bmal1 gene.


Bone & Joint Research
Vol. 13, Issue 4 | Pages 137 - 148
1 Apr 2024
Lu Y Ho T Huang C Yeh S Chen S Tsao Y

Aims

Pigment epithelium-derived factor (PEDF) is known to induce several types of tissue regeneration by activating tissue-specific stem cells. Here, we investigated the therapeutic potential of PEDF 29-mer peptide in the damaged articular cartilage (AC) in rat osteoarthritis (OA).

Methods

Mesenchymal stem/stromal cells (MSCs) were isolated from rat bone marrow (BM) and used to evaluate the impact of 29-mer on chondrogenic differentiation of BM-MSCs in culture. Knee OA was induced in rats by a single intra-articular injection of monosodium iodoacetate (MIA) in the right knees (set to day 0). The 29-mer dissolved in 5% hyaluronic acid (HA) was intra-articularly injected into right knees at day 8 and 12 after MIA injection. Subsequently, the therapeutic effect of the 29-mer/HA on OA was evaluated by the Osteoarthritis Research Society International (OARSI) histopathological scoring system and changes in hind paw weight distribution, respectively. The regeneration of chondrocytes in damaged AC was detected by dual-immunostaining of 5-bromo-2'-deoxyuridine (BrdU) and chondrogenic markers.


Bone & Joint Research
Vol. 7, Issue 1 | Pages 105 - 110
1 Jan 2018
Abar O Dharmar S Tang SY

Objectives. Advanced glycation end-products (AGEs) are a post-translational modification of collagen that form spontaneously in the skeletal matrix due to the presence of reducing sugars, such as glucose. The accumulation of AGEs leads to collagen cross-linking, which adversely affects bone quality and has been shown to play a major role in fracture risk. Thus, intervening in the formation and accumulation of AGEs may be a viable means of protecting bone quality. Methods. An in vitro model was used to examine the efficacy of two AGE-inhibitors, aminoguanidine (AG) and pyridoxamine (PM), on ageing human cortical bone. Mid-diaphyseal tibial cortical bone segments were obtained from female cadavers (n = 20, age range: 57 years to 97 years) and randomly subjected to one of four treatments: control; glucose only; glucose and AG; or glucose and PM. Following treatment, each specimen underwent mechanical testing under physiological conditions via reference point indentation, and AGEs were quantified by fluorescence. Results. Treatment with AG and PM showed a significant decrease in AGE content versus control groups, as well as a significant decrease in the change in indentation distance, a reliable parameter for analyzing bone strength, via two-way analysis of variance (ANOVA) (p < 0.05). Conclusions. The data suggest that AG and PM prevent AGE formation and subsequent biomechanical degradation in vitro. Modulation of AGEs may help to identify novel therapeutic targets to mitigate bone quality deterioration, especially deterioration due to ageing and in AGE-susceptible populations (e.g. diabetics). Cite this article: O. Abar, S. Dharmar, S. Y. Tang. The effect of aminoguanidine (AG) and pyridoxamine (PM) on ageing human cortical bone. Bone Joint Res 2018;7:105–110. DOI: 10.1302/2046-3758.71.BJR-2017-0135.R1