{"title":"Promotion of microfracture-mediated cartilage repair by the intra-articular injection of Mg2.","authors":"Zhian Chen, Tianhua Zhou, Zhengbo Yin, Peiya Duan, Ying Zhang, Yujiao Feng, Rongmao Shi, Yongqing Xu, Rongqing Pang, Hongbo Tan","doi":"10.1302/2046-3758.141.BJR-2024-0017.R2","DOIUrl":"10.1302/2046-3758.141.BJR-2024-0017.R2","url":null,"abstract":"<p><strong>Aims: </strong>Magnesium ions (Mg<sup>2+</sup>) play an important role in promoting cartilage repair in cartilage lesions. However, no research has focused on the role of Mg<sup>2+</sup> combined with microfracture (MFX) in hyaline-like cartilage repair mediated by cartilage injury. This study aimed to investigate the beneficial effects of the combination of MFX and Mg<sup>2+</sup> in cartilage repair.</p><p><strong>Methods: </strong>A total of 60 rabbits were classified into five groups (n = 12 each): sham, MFX, and three different doses of Mg<sup>2+</sup> treatment groups (0.05, 0.5, and 5 mol/L). Bone cartilage defects were created in the trochlear groove cartilage of rabbits. MFX surgery was performed after osteochondral defects. Mg<sup>2+</sup> was injected into knee joints immediately and two and four weeks after surgery. At six and 12 weeks after surgery, the rabbits were killed. Cartilage damage was detected by gross observation, micro-CT, and histological analysis. The expression levels of related genes were detected by real-time quantitative reverse transcription polymerase chain reaction (RT-qPCR).</p><p><strong>Results: </strong>The histological results showed that the 0.5 mol/L Mg<sup>2+</sup> group had deeper positive staining in haematoxylin-eosin (H&E), safranin O, Alcian blue, and type II collagen staining. The new cartilage coverage in the injury area was more complete, and the regeneration of hyaline cartilage was higher. The RT-qPCR results showed that sirtuin 1/bone morphogenetic protein-2/sex-determining region Y box 9 (SIRT1/BMP-2/SOX-9) and hypoxia-inducible factor 1-alpha (HIF-1α) messenger RNA levels were up-regulated after Mg<sup>2+</sup> injection.</p><p><strong>Conclusion: </strong>MFX combined with Mg<sup>2+</sup> treatment has a positive effect on cartilage repair. The Mg<sup>2+</sup> injection dose of 0.5 mol/L is most effective in enhancing microfracture-mediated cartilage repair.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"14 1","pages":"20-32"},"PeriodicalIF":4.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11737901/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Basic research for ultrasound-guided injection into skeletal muscle lesions in an experimental animal model.","authors":"Kiyomitsu Fujimoto, Takashi Kanamoto, Shunya Otani, Ryo Miyazaki, Kosuke Ebina, Ken Nakata","doi":"10.1302/2046-3758.141.BJR-2024-0090.R1","DOIUrl":"10.1302/2046-3758.141.BJR-2024-0090.R1","url":null,"abstract":"<p><strong>Aims: </strong>Ultrasound-guided injection techniques are expected to enhance therapeutic efficacy for skeletal muscle injuries and disorders, but basic knowledge is lacking. The purpose of this study was to examine the diagnostic accuracy of ultrasound for abnormal skeletal muscle lesions, and to examine the distribution patterns of solution and cells injected into abnormal muscle lesions under ultrasound guidance.</p><p><strong>Methods: </strong>A cardiotoxin (CTX)-induced muscle injury model was used. Briefly, CTX was injected into tibialis anterior muscle in rats under ultrasound observation. First, the diagnostic accuracy of abnormal muscle lesions on ultrasound was examined by comparing ultrasound findings and histology. Next, Fast Green solution and green fluorescent protein (GFP)-labelled cells were simultaneously injected into the abnormal muscle lesions under ultrasound guidance, and their distribution was evaluated.</p><p><strong>Results: </strong>Evaluation of short-axis ultrasound images and cross-sectional histological staining showed a strong correlation (r = 0.927; p < 0.001) between the maximum muscle damage area in ultrasound and haematoxylin and eosin (H&E) staining evaluations. Histological analysis showed that ultrasound-guided injection could successfully deliver Fast Green solution around the myofibres at the site of injury. In contrast, the distribution of injected cells was very localized compared to the area stained with Fast Green.</p><p><strong>Conclusion: </strong>This experimental animal study demonstrated the potential of ultrasound to quantitatively visualize abnormalities of skeletal muscle. It also showed that ultrasound-guided injections allowed for highly accurate distribution of solution and cells in abnormal muscle tissue, but the patterns of solution and cell distribution were markedly different. Although future studies using a more clinically relevant model are necessary, these results are important findings when considering biological therapies for skeletal muscle injuries and disorders.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"14 1","pages":"33-41"},"PeriodicalIF":4.7,"publicationDate":"2025-01-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11739951/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142999935","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Qualitative methods: the missing link in orthopaedic research.","authors":"Samantha Jones, Sarah Tyson","doi":"10.1302/2046-3758.141.BJR-2024-0501","DOIUrl":"10.1302/2046-3758.141.BJR-2024-0501","url":null,"abstract":"","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"14 1","pages":"16-19"},"PeriodicalIF":4.7,"publicationDate":"2025-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11734756/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142982606","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Reviewer acknowledgement.","authors":"Chloe E H Scott","doi":"10.1302/2046-3758.141.BJR-2025-00001","DOIUrl":"10.1302/2046-3758.141.BJR-2025-00001","url":null,"abstract":"","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"14 1","pages":"1-3"},"PeriodicalIF":4.7,"publicationDate":"2025-01-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11704814/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143762880","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bone & Joint ResearchPub Date : 2025-01-01DOI: 10.1302/2046-3758.141.BJR-2024-0191.R2
Maham Tanveer, Karina Klein, Brigitte von Rechenberg, Salim Darwiche, Hannah L Dailey
{"title":"Don't mind the gap: reframing the Perren strain rule for fracture healing using insights from virtual mechanical testing.","authors":"Maham Tanveer, Karina Klein, Brigitte von Rechenberg, Salim Darwiche, Hannah L Dailey","doi":"10.1302/2046-3758.141.BJR-2024-0191.R2","DOIUrl":"10.1302/2046-3758.141.BJR-2024-0191.R2","url":null,"abstract":"<p><strong>Aims: </strong>The \"2 to 10% strain rule\" for fracture healing has been widely interpreted to mean that interfragmentary strain greater than 10% predisposes a fracture to nonunion. This interpretation focuses on the gap-closing strain (axial micromotion divided by gap size), ignoring the region around the gap where osteogenesis typically initiates. The aim of this study was to measure gap-closing and 3D interfragmentary strains in plated ovine osteotomies and associate local strain conditions with callus mineralization.</p><p><strong>Methods: </strong>MicroCT scans of eight female sheep with plated mid-shaft tibial osteotomies were used to create image-based finite element models. Virtual mechanical testing was used to compute postoperative gap-closing and 3D continuum strains representing compression (volumetric strain) and shear deformation (distortional strain). Callus mineralization was measured in zones in and around the osteotomy gap.</p><p><strong>Results: </strong>Gap-closing strains averaged 51% (mean) at the far cortex. Peak compressive volumetric strain averaged 32% and only a small tissue volume (average 0.3 cm<sup>3</sup>) within the gap experienced compressive strains > 10%. Distortional strains were much higher and more widespread, peaking at a mean of 115%, with a mean of 3.3 cm<sup>3</sup> of tissue in and around the osteotomy experiencing distortional strains > 10%. Callus mineralization initiated outside the high-strain gap and was significantly lower within the fracture gap compared to around it at nine weeks.</p><p><strong>Conclusion: </strong>Ovine osteotomies can heal with high gap strains (> 10%) dominated by shear conditions. High gap strain appears to be a transient local limiter of osteogenesis, not a global inhibitor of secondary fracture repair.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"14 1","pages":"5-15"},"PeriodicalIF":4.7,"publicationDate":"2025-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11688128/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142909042","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Bone & Joint ResearchPub Date : 2024-12-16DOI: 10.1302/2046-3758.1312.BJR-2023-0272.R2
Hao Zou, Fei Hu, Xin Wu, Bin Xu, Guifeng Shang, Dong An, Dehao Qin, Xiaolei Zhang, Aofei Yang
{"title":"LINC01089 governs the miR-1287-5p/HSPA4 axis to negatively regulate osteogenic differentiation of mesenchymal stem cells.","authors":"Hao Zou, Fei Hu, Xin Wu, Bin Xu, Guifeng Shang, Dong An, Dehao Qin, Xiaolei Zhang, Aofei Yang","doi":"10.1302/2046-3758.1312.BJR-2023-0272.R2","DOIUrl":"10.1302/2046-3758.1312.BJR-2023-0272.R2","url":null,"abstract":"<p><strong>Aims: </strong>The involvement of long non-coding RNA (lncRNA) in bone marrow mesenchymal stem cell (MSC) osteogenic differentiation during osteoporosis (OP) development has attracted much attention. In this study, we aimed to disclose how LINC01089 functions in human mesenchymal stem cell (hMSC) osteogenic differentiation, and to study the mechanism by which LINC01089 regulates MSC osteogenesis.</p><p><strong>Methods: </strong>Quantitative reverse transcription polymerase chain reaction (RT-qPCR) and western blotting were performed to analyze LINC01089, miR-1287-5p, and heat shock protein family A (HSP70) member 4 (HSPA4) expression. The osteogenic differentiation of MSCs was assessed through alkaline phosphatase (ALP) activity, alizarin red S (ARS) staining, and by measuring the levels of osteogenic gene marker expressions using commercial kits and RT-qPCR analysis. Cell proliferative capacity was evaluated via the Cell Counting Kit-8 (CCK-8) assay. The binding of miR-1287-5p with LINC01089 and HSPA4 was verified by performing dual-luciferase reporter and RNA immunoprecipitation (RIP) experiments.</p><p><strong>Results: </strong>LINC01089 expression was reinforced in serum samples of OP patients, but it gradually diminished while hMSCs underwent osteogenic differentiation. LINC01089 knockdown facilitated hMSC osteogenic differentiation. This was substantiated by: the increase in ALP activity; ALP, runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), and osteopontin (OPN) messenger RNA (mRNA) levels; and level of ARS staining. Meanwhile, LINC01089 upregulation resulted in the opposite effects. LINC01089 targeted miR-1287-5p, and the LINC01089 knockdown-induced hMSC osteogenic differentiation was repressed by miR-1287-5p depletion. HSPA4 is a downstream function molecule of the LINC01089/miR-1287-5p pathway; miR-1287-5p negatively modulated HSPA4 levels and attenuated its functional effects.</p><p><strong>Conclusion: </strong>LINC01089 negatively regulated hMSC osteogenic differentiation, at least in part, via governing miR-1287-5p/HSPA4 signalling. These findings provide new insights into hMSC osteogenesis and bone metabolism.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 12","pages":"779-789"},"PeriodicalIF":4.7,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11648573/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142827337","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Long-term hypoxic atmosphere enhances the stemness, immunoregulatory functions, and therapeutic application of human umbilical cord mesenchymal stem cells.","authors":"Qi-Ming Huang, You-Qiong Zhuo, Zhong-Xin Duan, Yin-Lin Long, Jia-Nan Wang, Zhou-Hang Zhang, Shao-Yong Fan, Yong-Ming Huang, Ke-Yu Deng, Hong-Bo Xin","doi":"10.1302/2046-3758.1312.BJR-2024-0136.R2","DOIUrl":"10.1302/2046-3758.1312.BJR-2024-0136.R2","url":null,"abstract":"<p><strong>Aims: </strong>Mesenchymal stem cells (MSCs) are usually cultured in a normoxic atmosphere (21%) in vitro, while the oxygen concentrations in human tissues and organs are 1% to 10% when the cells are transplanted in vivo. However, the impact of hypoxia on MSCs has not been deeply studied, especially its translational application.</p><p><strong>Methods: </strong>In the present study, we investigated the characterizations of human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) in hypoxic (1%) and normoxic (21%) atmospheres with a long-term culture from primary to 30 generations, respectively. The comparison between both atmospheres systematically analyzed the biological functions of MSCs, mainly including stemness maintenance, immune regulation, and resistance to chondrocyte apoptosis, and studied their joint function and anti-inflammatory effects in osteoarthritis (OA) rats constructed by collagenase II.</p><p><strong>Results: </strong>We observed that long-term hypoxic culture surpassed normoxic atmosphere during hUC-MSCs culture in respect of promoting proliferation, anti-tumorigenicity, maintaining normal karyotype and stemness, inhibiting senescence, and improving immunoregulatory function and the role of anti-apoptosis in chondrocytes. Furthermore, we demonstrated that the transplantation of long-term hypoxic hUC-MSCs (Hy-MSCs) had a better therapeutic effect on OA rats compared with the hUC-MSCs cultured in the normoxic atmosphere (No-MSCs) in terms of the improved function and swelling recovery in the joints, and substantially inhibited the secretion of pro-inflammatory factors, which effectively alleviated cartilage damage by reducing the expression of matrix metallopeptidase 13 (MMP-13).</p><p><strong>Conclusion: </strong>Our results demonstrate that Hy-MSCs possess immense potential for clinical applications via promoting stemness maintenance and enhancing immunoregulatory function.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 12","pages":"764-778"},"PeriodicalIF":4.7,"publicationDate":"2024-12-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11634399/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142812153","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Effects of vitamin K supplementation on bone mineral density at different sites and bone metabolism in the middle-aged and elderly population.","authors":"Chenqi Xie, Jianbao Gong, Chenglong Zheng, Junwei Zhang, Jie Gao, Chunyan Tian, Xiaofei Guo, Shiyou Dai, Tianlin Gao","doi":"10.1302/2046-3758.1312.BJR-2024-0053.R1","DOIUrl":"10.1302/2046-3758.1312.BJR-2024-0053.R1","url":null,"abstract":"<p><strong>Aims: </strong>This meta-analysis and systematic review aimed to comprehensively investigate the effects of vitamin K supplementation on bone mineral density (BMD) at various sites and bone metabolism in middle-aged and older adults.</p><p><strong>Methods: </strong>The databases of PubMed, Web of Science, and Cochrane Library were thoroughly searched from inception to July 2023.</p><p><strong>Results: </strong>The results revealed that vitamin K supplementation increased BMD at the lumbar spine (p = 0.035). Moreover, the pooled effects demonstrated a notable increase in carboxylated osteocalcin (cOC) (p = 0.004), a decrease in uncarboxylated osteocalcin (ucOC) (p < 0.001), and no significant effect on total osteocalcin (tOC) (p = 0.076). Accordingly, the ratio of cOC to ucOC (p = 0.002) significantly increased, while the ratio of ucOC to tOC decreased (p = 0.043). However, there was no significant effect of vitamin K supplementation on other bone metabolism markers, such as cross-linked telopeptide of type 1 collagen (NTx), bone alkaline phosphatase (BAP), and procollagen I N-terminal propeptide (PINP). Subgroup analysis revealed that vitamin K notably enhanced bone health in females by increasing lumbar spine BMD (p = 0.028) and decreasing ucOC (p < 0.001). Vitamin K, especially vitamin K2, exhibited effects on maintaining or increasing lumbar spine BMD, and influencing the balance of cOC and ucOC.</p><p><strong>Conclusion: </strong>This review suggests that the beneficial effects of vitamin K supplementation on bone health primarily involve enhancing the carboxylation of OC rather than altering the total amount of OC.</p>","PeriodicalId":9074,"journal":{"name":"Bone & Joint Research","volume":"13 12","pages":"750-763"},"PeriodicalIF":4.7,"publicationDate":"2024-12-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11631259/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142806250","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}