Aims. Parathyroid hormone (PTH) (1-34) exhibits potential in preventing degeneration in both cartilage and subchondral bone in osteoarthritis (OA) development. We assessed the effects of PTH (1-34) at different concentrations on bone and cartilage metabolism in a collagenase-induced mouse model of OA and examined whether PTH (1-34) affects the JAK2/STAT3 signalling pathway in this process. Methods. Collagenase-induced OA was established in C57Bl/6 mice. Therapy with PTH (1-34) (10 μg/kg/day or 40 μg/kg/day) was initiated immediately after surgery and continued for six weeks. Cartilage pathology was evaluated by gross visual, histology, and immunohistochemical assessments. Cell apoptosis was analyzed by TUNEL staining. Microcomputed tomography (micro-CT) was used to evaluate the bone mass and the microarchitecture in subchondral bone. Results. Enhanced matrix catabolism, increased apoptosis of chondrocytes in cartilage, and overexpressed JAK2/STAT3 and p-JAK2/p-STAT3 were observed in cartilage in this model. All of these changes were prevented by PTH (1-34) treatment, with no significant difference between the low-dose and high-dose groups. Micro-CT analysis indicated that bone mineral density (BMD), bone volume/trabecular volume (BV/TV), and trabecular thickness (Tb.Th) levels were significantly lower in the OA group than those in the Sham, PTH 10 μg, and PTH 40 μg groups, but these parameters were significantly higher in the PTH 40 μg group than in the PTH 10 μg group. Conclusion. Intermittent administration of PTH (1-34) exhibits protective effects on both cartilage and subchondral bone in a dose-dependent manner on the latter in a collagenase-induced OA mouse model, which may be involved in regulating the JAK2/STAT3 signalling pathway. Cite this article: Bone Joint Res 2020;9(10):675–688

Aims. Acridine orange (AO) demonstrates several biological activities. When exposed to low doses of X-ray radiation, AO increases the production of reactive radicals (radiodynamic therapy (AO-RDT)). We elucidated the efficacy of AO-RDT in breast and prostate cancer cell lines, which are likely to develop bone metastases. Methods. We used the mouse osteosarcoma cell line LM8, the human breast cancer cell line MDA-MB-231, and the human prostate cancer cell line PC-3. Cultured cells were exposed to AO and radiation at various concentrations followed by various doses of irradiation. The cell viability was then measured. In vivo, each cell was inoculated subcutaneously into the backs of mice. In the AO-RDT group, AO (1.0 μg) was locally administered subcutaneously around the tumour followed by 5 Gy of irradiation. In the radiation group, 5 Gy of irradiation alone was administered after macroscopic tumour formation. The mice were killed on the 14th day after treatment. The change in tumour volume by AO-RDT was primarily evaluated. Results. The viability of LM8, MDA-MB-231, and PC-3 cells strongly decreased at AO concentration of 1.0 μg/ml and a radiation dose of 5 Gy. In xenograft mouse model, the AO-RDT also showed a strong cytocidal effect on tumour at the backside in osteosarcoma, breast cancer, and prostate cancer. AO-RDT treatment was more effective for tumour control than radiotherapy in breast cancer. Conclusion. AO-RDT was effective in preventing the proliferation of osteosarcoma, breast cancer, and prostate cancer cell lines in vitro. The reduction in tumour volume by AO-RDT was also confirmed in vivo. Cite this article: Bone Joint Res 2022;11(10):715–722

Aims. Periprosthetic joint infections (PJIs) are rare, but represent a great burden for the patient. In addition, the incidence of methicillin-resistant Staphylococcus aureus (MRSA) is increasing. The aim of this rat experiment was therefore to compare the antibiotics commonly used in the treatment of PJIs caused by MRSA. Methods. For this purpose, sterilized steel implants were implanted into the femur of 77 rats. The metal devices were inoculated with suspensions of two different MRSA strains. The animals were divided into groups and treated with vancomycin, linezolid, cotrimoxazole, or rifampin as monotherapy, or with combination of antibiotics over a period of 14 days. After a two-day antibiotic-free interval, the implant was explanted, and bone, muscle, and periarticular tissue were microbiologically analyzed. Results. Vancomycin and linezolid were able to significantly (p < 0.05) reduce the MRSA bacterial count at implants. No significant effect was found at the bone. Rifampin was the only monotherapy that significantly reduced the bacterial count on implant and bone. The combination with vancomycin or linezolid showed significant efficacy. Treatment with cotrimoxazole alone did not achieve a significant bacterial count reduction. The combination of linezolid plus rifampin was significantly more effective on implant and bone than the control group in both trials. Conclusion. Although rifampicin is effective as a monotherapy, it should not be used because of the high rate of resistance development. Our animal experiments showed the great importance of combination antibiotic therapies. In the future, investigations with higher case numbers, varied bacterial concentrations, and changes in individual drug dosages will be necessary to be able to draw an exact comparison, possibly within a clinical trial. Cite this article: Bone Joint Res 2022;11(3):143–151

Aims. The decrease in the number of satellite cells (SCs), contributing to myofibre formation and reconstitution, and their proliferative capacity, leads to muscle loss, a condition known as sarcopenia. Resistance training can prevent muscle loss; however, the underlying mechanisms of resistance training effects on SCs are not well understood. We therefore conducted a comprehensive transcriptome analysis of SCs in a mouse model. Methods. We compared the differentially expressed genes of SCs in young mice (eight weeks old), middle-aged (48-week-old) mice with resistance training intervention (MID+ T), and mice without exercise (MID) using next-generation sequencing and bioinformatics. Results. After the bioinformatic analysis, the PI3K-Akt signalling pathway and the regulation of actin cytoskeleton in particular were highlighted among the top ten pathways with the most differentially expressed genes involved in the young/MID and MID+ T/MID groups. The expression of Gng5, Atf2, and Rtor in the PI3K-Akt signalling pathway was higher in the young and MID+ T groups compared with the MID group. Similarly, Limk1, Arhgef12, and Araf in the regulation of the actin cytoskeleton pathway had a similar bias. Moreover, the protein expression profiles of Atf2, Rptor, and Ccnd3 in each group were paralleled with the results of NGS. Conclusion. Our results revealed that age-induced muscle loss might result from age-influenced genes that contribute to muscle development in SCs. After resistance training, age-impaired genes were reactivated, and age-induced genes were depressed. The change fold in these genes in the young/MID mice resembled those in the MID + T/MID group, suggesting that resistance training can rejuvenate the self-renewing ability of SCs by recovering age-influenced genes to prevent sarcopenia. Cite this article: Bone Joint Res 2022;11(2):121–133

Aims. Distraction osteogenesis (DO) is a useful orthopaedic procedure employed to lengthen and reshape bones by stimulating bone formation through controlled slow stretching force. Despite its promising applications, difficulties are still encountered. Our previous study demonstrated that pulsed electromagnetic field (PEMF) treatment significantly enhances bone mineralization and neovascularization, suggesting its potential application. The current study compared a new, high slew rate (HSR) PEMF signal, with different treatment durations, with the standard Food and Drug Administration (FDA)-approved signal, to determine if HSR PEMF is a better alternative for bone formation augmentation. Methods. The effects of a HSR PEMF signal with three daily treatment durations (0.5, one, and three hours/day) were investigated in an established rat DO model with comparison of an FDA-approved classic signal (three hrs/day). PEMF treatments were applied to the rats daily for 35 days, starting from the distraction phase until termination. Radiography, micro-CT (μCT), biomechanical tests, and histological examinations were employed to evaluate the quality of bone formation. Results. All rats tolerated the treatment well and no obvious adverse effects were found. By comparison, the HSR signal (three hrs/day) treatment group achieved the best healing outcome, in that endochondral ossification and bone consolidation were enhanced. In addition, HSR signal treatment (one one hr/day) had similar effects to treatment using the classic signal (three three hrs/day), indicating that treatment duration could be significantly shortened with the HSR signal. Conclusion. HSR signal may significantly enhance bone formation and shorten daily treatment duration in DO, making it a potential candidate for a new clinical protocol for patients undergoing DO treatments. Cite this article: Bone Joint Res 2021;10(12):767–779

Aims. This study aimed to investigate the role and mechanism of meniscal cell lysate (MCL) in fibroblast-like synoviocytes (FLSs) and osteoarthritis (OA). Methods. Meniscus and synovial tissue were collected from 14 patients with and without OA. MCL and FLS proteins were extracted and analyzed by liquid chromatography‒mass spectrometry (LC‒MS). The roles of MCL and adenine nucleotide translocase 3 (ANT3) in FLSs were examined by enzyme-linked immunosorbent assay (ELISA), flow cytometry, immunofluorescence, and transmission electron microscopy. Histological analysis was performed to determine ANT3 expression levels in a male mouse model. Results. We discovered for the first time that MCL was substantially enriched in the synovial fluid of OA patients and promoted the release of inflammatory cytokines from FLSs through MCL phagocytosis. Through LC‒MS, ANT3 was identified and determined to be significantly upregulated in MCL and OA-FLSs, corresponding to impaired mitochondrial function and cell viability in OA-FLSs. Mitochondrial homeostasis was restored by ANT3 suppression, thereby alleviating synovial inflammation. Furthermore, elevated ANT3 levels inhibited ERK phosphorylation. Specifically, silencing ANT3 prevented inhibition of ERK phosphorylation and significantly reduced the elevation of reactive oxygen species (ROS) and JC1 membrane potential in MCL-induced synovial inflammation. Conclusion. This study revealed the important roles of MCL and ANT3 in FLS mitochondria. Silencing ANT3 rescued ERK phosphorylation, thereby restoring mitochondrial homeostasis in FLSs and alleviating synovitis and OA development, offering a potential target for treating synovitis and preventing early-stage OA. Cite this article: Bone Joint Res 2023;12(4):274–284

Aims. Osteoarthritis (OA) is the most common chronic pathema of human joints. The pathogenesis is complex, involving physiological and mechanical factors. In previous studies, we found that ferroptosis is intimately related to OA, while the role of Sat1 in chondrocyte ferroptosis and OA, as well as the underlying mechanism, remains unclear. Methods. In this study, interleukin-1β (IL-1β) was used to simulate inflammation and Erastin was used to simulate ferroptosis in vitro. We used small interfering RNA (siRNA) to knock down the spermidine/spermine N1-acetyltransferase 1 (Sat1) and arachidonate 15-lipoxygenase (Alox15), and examined damage-associated events including inflammation, ferroptosis, and oxidative stress of chondrocytes. In addition, a destabilization of the medial meniscus (DMM) mouse model of OA induced by surgery was established to investigate the role of Sat1 inhibition in OA progression. Results. The results showed that inhibition of Sat1 expression can reduce inflammation, ferroptosis changes, reactive oxygen species (ROS) level, and lipid-ROS accumulation induced by IL-1β and Erastin. Knockdown of Sat1 promotes nuclear factor-E2-related factor 2 (Nrf2) signalling. Additionally, knockdown Alox15 can alleviate the inflammation-related protein expression induced by IL-1β and ferroptosis-related protein expression induced by Erastin. Furthermore, knockdown Nrf2 can reverse these protein expression alterations. Finally, intra-articular injection of diminazene aceturate (DA), an inhibitor of Sat1, enhanced type II collagen (collagen II) and increased Sat1 and Alox15 expression. Conclusion. Our results demonstrate that inhibition of Sat1 could alleviate chondrocyte ferroptosis and inflammation by downregulating Alox15 activating the Nrf2 system, and delaying the progression of OA. These findings suggest that Sat1 provides a new approach for studying and treating OA. Cite this article: Bone Joint Res 2024;13(3):110–123

Aims. This study aimed to investigate whether human umbilical cord mesenchymal stem cells (UC-MSCs) can prevent articular cartilage degradation and explore the underlying mechanisms in a rat osteoarthritis (OA) model induced by monosodium iodoacetate (MIA). Methods. Human UC-MSCs were characterized by their phenotype and multilineage differentiation potential. Two weeks after MIA induction in rats, human UC-MSCs were intra-articularly injected once a week for three weeks. The therapeutic effect of human UC-MSCs was evaluated by haematoxylin and eosin, toluidine blue, Safranin-O/Fast green staining, and Mankin scores. Markers of joint cartilage injury and pro- and anti-inflammatory markers were detected by immunohistochemistry. Results. Histopathological analysis showed that intra-articular injection of human UC-MSCs significantly inhibited the progression of OA, as demonstrated by reduced cartilage degradation, increased Safranin-O staining, and lower Mankin scores. Immunohistochemistry showed that human UC-MSC treatment down-regulated the expression of matrix metalloproteinase-13 (MMP13) and a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5), and enhanced the expression of type II collagen and ki67 in the articular cartilage. Furthermore, human UC-MSCs significantly decreased the expression of interleukin (IL)-1β and tumour necrosis factor-α (TNF-α), while increasing TNF-α-induced protein 6 and IL-1 receptor antagonist. Conclusion. Our results demonstrated that human UC-MSCs ameliorate MIA-induced OA by preventing cartilage degradation, restoring the proliferation of chondrocytes, and inhibiting the inflammatory response, which implies that human UC-MSCs may be a promising strategy for the treatment of OA. Cite this article: Bone Joint Res 2021;10(3):226–236

Aims. MicroRNA-183 (miR-183) is known to play important roles in osteoarthritis (OA) pain. The aims of this study were to explore the specific functions of miR-183 in OA pain and to investigate the underlying mechanisms. Methods. Clinical samples were collected from patients with OA, and a mouse model of OA pain was constructed by surgically induced destabilization of the medial meniscus (DMM). Reverse transcription quantitative polymerase chain reaction was employed to measure the expression of miR-183, transforming growth factor α (TGFα), C-C motif chemokine ligand 2 (CCL2), proinflammatory cytokines (interleukin (IL)-6, IL-1β, and tumour necrosis factor-α (TNF-α)), and pain-related factors (transient receptor potential vanilloid subtype-1 (TRPV1), voltage-gated sodium 1.3, 1.7, and 1.8 (Nav1.3, Nav1.7, and Nav1.8)). Expression of miR-183 in the dorsal root ganglia (DRG) of mice was evaluated by in situ hybridization. TGFα, CCL2, and C-C chemokine receptor type 2 (CCR2) levels were examined by immunoblot analysis and interaction between miR-183 and TGFα, determined by luciferase reporter assay. The extent of pain in mice was measured using a behavioural assay, and OA severity assessed by Safranin O and Fast Green staining. Immunofluorescent staining was conducted to examine the infiltration of macrophages in mouse DRG. Results. miR-183 was downregulated in tissue samples from patients and mice with OA. In DMM mice, overexpression of miR-183 inhibited the expression of proinflammatory cytokines (IL-6, IL-1β, TNF-α) and pain-related factors (TRPV1, Nav1.3, Nav1.7, Nav1.8) in DRG. OA pain was relieved by miR-183-mediated inhibition of macrophage infiltration, and dual luciferase reporter assay demonstrated that miR-183 directly targeted TGFα. Conclusion. Our data demonstrate that miR-183 can ameliorate OA pain by inhibiting the TGFα-CCL2/CCR2 signalling axis, providing an excellent therapeutic target for OA treatment. Cite this article: Bone Joint Res 2021;10(8):548–557

Aims. Acquired heterotopic ossification (HO) is a debilitating disease characterized by abnormal extraskeletal bone formation within soft-tissues after injury. The exact pathogenesis of HO remains unknown. It was reported that BRD4 may contribute to osteoblastic differentiation. The current study aims to determine the role of BRD4 in the pathogenesis of HO and whether it could be a potential target for HO therapy. Methods. Achilles tendon puncture (ATP) mouse model was performed on ten-week-old male C57BL/6J mice. One week after ATP procedure, the mice were given different treatments (e.g. JQ1, shMancr). Achilles tendon samples were collected five weeks after treatment for RNA-seq and real-time quantitative polymerase chain reaction (RT-qPCR) analysis; the legs were removed for micro-CT imaging and subsequent histology. Human bone marrow mesenchymal stem cells (hBMSCs) were isolated and purified bone marrow collected during surgeries by using density gradient centrifugation. After a series of interventions such as knockdown or overexpressing BRD4, Alizarin red staining, RT-qPCR, and Western Blot (Runx2, alkaline phosphatase (ALP), Osx) were performed on hBMSCs. Results. Overexpression of BRD4 enhanced while inhibition of Brd4 suppressed the osteogenic differentiation of hBMSCs in vitro. Overexpression of Brd4 increased the expression of mitotically associated long non-coding RNA (Mancr). Downregulation of Mancr suppressed the osteoinductive effect of BRD4. In vivo, inhibition of BRD4 by JQ1 significantly attenuated pathological bone formation in the ATP model (p = 0.001). Conclusion. BRD4 was found to be upregulated in HO and Brd4-Mancr-Runx2 signalling was involved in the modulation of new bone formation in HO. Cite this article: Bone Joint Res 2021;10(10):668–676

Aims. In the context of tendon degenerative disorders, the need for innovative conservative treatments that can improve the intrinsic healing potential of tendon tissue is progressively increasing. In this study, the role of pulsed electromagnetic fields (PEMFs) in improving the tendon healing process was evaluated in a rat model of collagenase-induced Achilles tendinopathy. Methods. A total of 68 Sprague Dawley rats received a single injection of type I collagenase in Achilles tendons to induce the tendinopathy and then were daily exposed to PEMFs (1.5 mT and 75 Hz) for up to 14 days - starting 1, 7, or 15 days after the injection - to identify the best treatment option with respect to the phase of the disease. Then, 7 and 14 days of PEMF exposure were compared to identify the most effective protocol. Results. The daily exposure to PEMFs generally provided an improvement in the fibre organization, a decrease in cell density, vascularity, and fat deposition, and a restoration of the physiological cell morphology compared to untreated tendons. These improvements were more evident when the tendons were exposed to PEMFs during the mid-acute phase of the pathology (7 days after induction) rather than during the early (1 day after induction) or the late acute phase (15 days after induction). Moreover, the exposure to PEMFs for 14 days during the mid-acute phase was more effective than for 7 days. Conclusion. PEMFs exerted a positive role in the tendon healing process, thus representing a promising conservative treatment for tendinopathy, although further investigations regarding the clinical evaluation are needed. Cite this article: Bone Joint Res 2020;9(9):613–622

The aim of our study was to investigate the effect of platelet-rich plasma on the proliferation and differentiation of rat bone-marrow cells and to determine an optimal platelet concentration in plasma for osseous tissue engineering. Rat bone-marrow cells embedded in different concentrations of platelet-rich plasma gel were cultured for six days. Their potential for proliferation and osteogenic differentiation was analysed. Using a rat limb-lengthening model, the cultured rat bone-marrow cells with platelet-rich plasma of variable concentrations were transplanted into the distraction gap and the quality of the regenerate bone was evaluated radiologically. Cellular proliferation was enhanced in all the platelet-rich plasma groups in a dose-dependent manner. Although no significant differences in the production and mRNA expression of alkaline phosphatase were detected among these groups, mature bone regenerates were more prevalent in the group with the highest concentration of platelets. Our results indicate that a high platelet concentration in the platelet-rich plasma in combination with osteoblastic cells could accelerate the formation of new bone during limb-lengthening procedures

Aims. Bone metastasis ultimately occurs due to a complex multistep process, during which the interactions between cancer cells and bone microenvironment play important roles. Prior to colonization of the bone, cancer cells must succeed through a series of steps that will allow them to gain migratory and invasive properties; epithelial-to-mesenchymal transition (EMT) is known to be integral here. The aim of this study was to determine the effects of G protein subunit alpha Q (GNAQ) on the mechanisms underlying bone metastasis through EMT pathway. Methods. A total of 80 tissue samples from patients who were surgically treated during January 2012 to December 2014 were used in the present study. Comparative gene analysis revealed that the GNAQ was more frequently altered in metastatic bone lesions than in primary tumour sites in lung cancer patients. We investigated the effects of GNAQ on cell proliferation, migration, EMT, and stem cell transformation using lung cancer cells with GNAQ-knockdown. A xenograft mouse model tested the effect of GNAQ using micro-CT analyses and histological analyses. Results. GNAQ-knockdown showed down-regulation of tumour growth through mitogen-activated protein kinase (MAPK) signalling in lung cancer cells, but not increased apoptosis. We found that GNAQ-knockdown induced EMT and promoted invasiveness. GNAQ-knockdown cells injected into the bone marrow of murine tibia induced tumour growth and bone-to-lung metastasis, whereas it did not in control mice. Moreover, the knockdown of GNAQ enhanced cancer stem cell-like properties in lung cancer cells, which resulted in the development of resistance to chemotherapy. Conclusion. The present study reveals that the GNAQ-knockdown induced cancer stem cell-like properties. Cite this article: Bone Joint Res 2021;10(5):310–320

Objectives. We have observed clinical cases where bone is formed in the overlaying muscle covering surgically created bone defects treated with a hydroxyapatite/calcium sulphate biomaterial. Our objective was to investigate the osteoinductive potential of the biomaterial and to determine if growth factors secreted from local bone cells induce osteoblastic differentiation of muscle cells. Materials and Methods. We seeded mouse skeletal muscle cells C2C12 on the hydroxyapatite/calcium sulphate biomaterial and the phenotype of the cells was analysed. To mimic surgical conditions with leakage of extra cellular matrix (ECM) proteins and growth factors, we cultured rat bone cells ROS 17/2.8 in a bioreactor and harvested the secreted proteins. The secretome was added to rat muscle cells L6. The phenotype of the muscle cells after treatment with the media was assessed using immunostaining and light microscopy. Results. C2C12 cells differentiated into osteoblast-like cells expressing prominent bone markers after seeding on the biomaterial. The conditioned media of the ROS 17/2.8 contained bone morphogenetic protein-2 (BMP-2 8.4 ng/mg, standard deviation (. sd. ) 0.8) and BMP-7 (50.6 ng/mg, . sd. 2.2). In vitro, this secretome induced differentiation of skeletal muscle cells L6 towards an osteogenic lineage. Conclusion. Extra cellular matrix proteins and growth factors leaking from a bone cavity, along with a ceramic biomaterial, can synergistically enhance the process of ectopic ossification. The overlaying muscle acts as an osteoinductive niche, and provides the required cells for bone formation. Cite this article: D. B. Raina, A. Gupta, M. M. Petersen, W. Hettwer, M. McNally, M. Tägil, M-H. Zheng, A. Kumar, L. Lidgren. Muscle as an osteoinductive niche for local bone formation with the use of a biphasic calcium sulphate/hydroxyapatite biomaterial. Bone Joint Res 2016;5:500–511. DOI: 10.1302/2046-3758.510.BJR-2016-0133.R1

Objectives. Our objective in this article is to test the hypothesis that type 2 diabetes mellitus (T2DM) is a factor in the onset and progression of osteoarthritis, and to characterise the quality of the articular cartilage in an appropriate rat model. Methods. T2DM rats were obtained from the UC Davis group and compared with control Lewis rats. The diabetic rats were sacrificed at ages from six to 12 months, while control rats were sacrificed at six months only. Osteoarthritis severity was determined via histology in four knee quadrants using the OARSI scoring guide. Immunohistochemical staining was also performed as a secondary form of osteoarthritic analysis. Results. T2DM rats had higher mean osteoarthritis scores than the control rats in each of the four areas that were analysed. However, only the results at the medial and lateral femur and medial tibia were significant. Cysts were also found in T2DM rats at the junction of the articular cartilage and subchondral bone. Immunohistochemical analysis does not show an increase in collagen II between control and T2DM rats. Mass comparisons also showed a significant relationship between mass and osteoarthritis score. Conclusions. T2DM was found to cause global degeneration in the UCD rat knee joints, suggesting that diabetes itself is a factor in the onset and progression of osteoarthritis. The immunohistochemistry stains showed little to no change in collagen II degeneration between T2DM and control rats. Overall, it seems that the animal model used is pertinent to future studies of T2DM in the development and progression of osteoarthritis. Cite this article: Bone Joint Res 2014;3:203–11

Objectives. The role of mechanical stress and transforming growth factor beta 1 (TGF-β1) is important in the initiation and progression of osteoarthritis (OA). However, the underlying molecular mechanisms are not clearly known. Methods. In this study, TGF-β1 from osteoclasts and knee joints were analyzed using a co-cultured cell model and an OA rat model, respectively. Five patients with a femoral neck fracture (four female and one male, mean 73.4 years (68 to 79)) were recruited between January 2015 and December 2015. Results showed that TGF-β1 was significantly upregulated in osteoclasts by cyclic loading in a time- and dose-dependent mode. The osteoclasts were subjected to cyclic loading before being co-cultured with chondrocytes for 24 hours. Results. A significant decrease in the survival rate of co-cultured chondrocytes was found. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labelling (TUNEL) assay demonstrated that mechanical stress-induced apoptosis occurred significantly in co-cultured chondrocytes but administration of the TGF-β1 receptor inhibitor, SB-505124, can significantly reverse these effects. Abdominal administration of SB-505124 can attenuate markedly articular cartilage degradation in OA rats. Conclusion. Mechanical stress-induced overexpression of TGF-β1 from osteoclasts is responsible for chondrocyte apoptosis and cartilage degeneration in OA. Administration of a TGF-β1 inhibitor can inhibit articular cartilage degradation. Cite this article: R-K. Zhang, G-W. Li, C. Zeng, C-X. Lin, L-S. Huang, G-X. Huang, C. Zhao, S-Y. Feng, H. Fang. Mechanical stress contributes to osteoarthritis development through the activation of transforming growth factor beta 1 (TGF-β1). Bone Joint Res 2018;7:587–594. DOI: 10.1302/2046-3758.711.BJR-2018-0057.R1

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 Res 2018;7:289–297. DOI: 10.1302/2046-3758.74.BJR-2017-0302.R1

Aims

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