Bone最新文献

{"title":"Morphology and spatial distribution of cortical bone canals: Evaluation of shape parameters, lacunarity, and fractal dimension in the human irradiated mandible","authors":"Karin Berria Tomazelli ,&nbsp;Bianca Carla Bianco ,&nbsp;Barbara Rech de Castro ,&nbsp;Isabela Ramos ,&nbsp;Vithória Rabelo Zimmer ,&nbsp;Priscila Barbosa Ferreira Soares ,&nbsp;Liliane Janete Grando ,&nbsp;Gustavo Davi Rabelo","doi":"10.1016/j.bone.2024.117349","DOIUrl":"10.1016/j.bone.2024.117349","url":null,"abstract":"<div><div>This study aimed to assess the spatial distribution of cortical bone canals' network through the analysis of lacunarity (Lac), fractal dimension (FD), and canal morphological parameters in the mandible (IR group, n = 7) of human patients under radiotherapy in comparison with non-irradiated younger (yC group, n = 8) and older (oC group, n = 8) individuals. Patients who underwent mandibular surgery were selected to have bone fragments removed during surgery, and undecalcified histological slides were analyzed by phase-contrast microscopy by two operators. The following morphological parameters were assessed in the Haversian canal (Ca): area (Ca·Ar, μm²), perimeter (Ca·Pm, μm), and circularity (Ca.c, #). Binary images were obtained by manually segmenting canals for Lac and FD analysis through box-counting. A total of 273 canals were segmented in the IR group, 284 in the yC group, and 60 in the oC group. Higher values for canal area and perimeter (p &lt; 0.0001) were found for oC (7871 μm² and 358.9 μm, respectively), followed by IR (2958 μm² and 212.9 μm, respectively), and yC (1286 μm² and 135.8 μm, respectively). Canal circularity was lower for oC (p &lt; 0.0001). Lac and FD did not differ when comparing irradiated individuals with the younger and older individuals. In conclusion, cortical canals are morphologically different when comparing younger and older individuals with patients exposed to ionizing radiation. Alterations on Haversian canals after radiotherapy could have clinical implications, mostly related to vascularization. Lac and FD were reliable parameters in assessing the spatial organization of the canals within the matrix.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"192 ","pages":"Article 117349"},"PeriodicalIF":3.5,"publicationDate":"2024-11-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142756047","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Association of Glucagon-like peptide-1 receptor agonists use with fracture risk in type 2 diabetes: A meta-analysis of randomized controlled trials","authors":"Yuan Zhang ,&nbsp;Guanhua Chen ,&nbsp;Weimin Wang ,&nbsp;Donghui Yang ,&nbsp;Dalong Zhu ,&nbsp;Yali Jing","doi":"10.1016/j.bone.2024.117338","DOIUrl":"10.1016/j.bone.2024.117338","url":null,"abstract":"<div><h3>Background</h3><div>Type 2 diabetes mellitus (T2DM) is associated with an increased risk of osteoporosis (OP) and fractures.</div></div><div><h3>Purpose</h3><div>The aim of this study was to analyze the available evidence on the effect of GLP-1 RAs on fracture risk in patients with type 2 diabetes.</div></div><div><h3>Methods</h3><div>A systematic search based on PubMed, Embase and Web of Science databases was performed to collect relevant literature published until May 2024 on the application of GLP-1 RAs in T2DM patients. Data were extracted from each study for comparative analysis, and meta-analysis was performed using R software to calculate relative risk (RR) and 95 % confidence intervals (CI) for dichotomous variables. Two subgroup analyses were also performed.</div></div><div><h3>Results</h3><div>A total of 44 randomized controlled trials (RCTs) involving 47,823 patients were analyzed. There were 292 incident fracture cases (138 in GLP-1 RAs group and 154 in control group). The pooled RR for fractures in patients treated with GLP-1RAs compared with those treated with placebo or other anti-diabetic drugs was 0.77 (95 % CI: 0.61–0.96). Subgroup analyses showed that the beneficial effect was dependent on the period of treatment with GLP-1 RAs, only treated for &gt;78 weeks were effective in reducing the risk of fractures in patients with T2DM (RR 0.77; 95 % CI: 0.61–0.96). Furthermore, subgroup analyses showed that liraglutide treatment was associated with a significant reduction in fracture risk (RR 0.42; 95 % CI: 0.21–0.85). However, other GLP-1 RAs did not present benefits over other anti-diabetic drug treatments.</div></div><div><h3>Conclusion</h3><div>GLP-1 RAs could reduce the risk of fracture in T2DM patients, and the beneficial effect was interrelated to the period of treatment. Liraglutide could significantly reduce the risk of fracture in T2DM patients compared to placebo and other anti-diabetic drugs. Due to the limited nature of contemporary research, further studies are needed to develop a clear clinical consensus.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"192 ","pages":"Article 117338"},"PeriodicalIF":3.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741722","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone remodelling after scaphoid fractures: HR-pQCT, clinical and laboratory data from a prospective 1-year follow-up study","authors":"Stefan Benedikt ,&nbsp;Kerstin Stock ,&nbsp;Lukas Horling ,&nbsp;Gernot Schmidle ,&nbsp;Michael Schirmer ,&nbsp;Gerald Degenhart ,&nbsp;Michael Blauth ,&nbsp;Claudia Lamina ,&nbsp;Johannes Dominikus Pallua ,&nbsp;Rohit Arora","doi":"10.1016/j.bone.2024.117337","DOIUrl":"10.1016/j.bone.2024.117337","url":null,"abstract":"<div><h3>Introduction</h3><div>The exact mechanisms of bone remodelling after scaphoid fractures are not fully understood. Blood supply may lead to delayed consolidation and non-unions as challenging long-term problems. The aim of this study was to follow-up the microstructure during the scaphoid bone remodelling process using High Resolution peripheral Quantitative Computed Tomography (HR-pQCT) and compare the results with clinical and laboratory data.</div></div><div><h3>Patients and methods</h3><div>In this monocentric, prospective, controlled, clinical trial 39 patients with an unilateral conservatively treated scaphoid fracture at the level of the waist or the distal pole were followed up over one year (2, 4, 6, 12, 26 and 52 weeks after trauma). Fracture healing was monitored by clinical examination, blood bone remodelling markers and HR-pQCT.</div></div><div><h3>Results</h3><div>The HR-pQCT showed significant changes in trabecular number, trabecular thickness, trabecular separation and bone mineral density until the 52 week follow-up. Complete bony consolidation on HR-pQCT was evident in half of the fractures at 12 weeks and in all fractures at 52 weeks after trauma. None of the patients developed a non-union. Carboxy-terminal collagen crosslinks as resorption marker showed significant changes until the 52 week follow-up.</div></div><div><h3>Conclusion</h3><div>This study shows detailed clinical, laboratory and radiologic changes during follow-up of uncomplicated fracture healing of conservative scaphoids. Bony consolidation is highly variable and can take up to one year after fracture. Larger studies are warranted, as HR-pQCT might provide detailed microstructural information to better predict fracture healing processes, thus acting as a high-resolution and low-radiation alternative to standard conventional CT.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"192 ","pages":"Article 117337"},"PeriodicalIF":3.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741741","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":"Osteocytic oxygen sensing: Distinct impacts of VHL and HIF-2alpha on bone integrity","authors":"Sarah V. Mendoza ,&nbsp;Kristina V. Wells ,&nbsp;Deepa K. Murugesh ,&nbsp;Nicholas R. Hum ,&nbsp;Aimy Sebastian ,&nbsp;Bria M. Gorman ,&nbsp;Alice Wong ,&nbsp;Benjamin Osipov ,&nbsp;Blaine A. Christiansen ,&nbsp;Gabriela G. Loots ,&nbsp;Alexander G. Robling ,&nbsp;Clare E. Yellowley ,&nbsp;Damian C. Genetos","doi":"10.1016/j.bone.2024.117339","DOIUrl":"10.1016/j.bone.2024.117339","url":null,"abstract":"<div><div>Skeletal fracture resistance emerges from multiple components of bone structure like microarchitecture, matrix mineralization, and organization. These characteristics are engendered <em>via</em> mechanisms like the hypoxia-inducible factors (HIF) pathway, involving two paralogs, HIF-1α and HIF-2α. Under normoxia, HIF-α is targeted for degradation <em>via</em> von-Hippel Lindau (VHL); hypoxia enables HIF-α stabilization and induction of target genes. We previously showed that osteocytic Vhl deletion or expression of degradation-resistant HIF-2α cDR female mice each produced high bone mass, whereas degradation-resistant osteocytic HIF-1α produced no overt phenotype. We report within that Vhl cKO increased bone strength, while HIF-2α cDR displayed markedly reduced bone strength below Cre-negative controls. This suggests that VHL and HIF-2α drive distinct responses that promote disparate effects on bone strength. Both Vhl deletion or HIF-2α accumulation generated two discrete bone morphologies: an outer lamellar cortex and a woven, poorly mineralized endocortex that imparted dramatically different functional outcomes. Our studies reveal novel influence of osteocytic HIF-2α signaling on collagen matrix organization, mineralization, and bone strength.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"192 ","pages":"Article 117339"},"PeriodicalIF":3.5,"publicationDate":"2024-11-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142741743","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":"Three-dimensional cranial suture morphometric changes in young rats during normal growth","authors":"Tsolmonbaatar Khurelbaatar ,&nbsp;Leah Fisher ,&nbsp;Lindsey Westover ,&nbsp;Michael R. Doschak ,&nbsp;Dan L. Romanyk","doi":"10.1016/j.bone.2024.117336","DOIUrl":"10.1016/j.bone.2024.117336","url":null,"abstract":"<div><div>The age-based morphometric changes of cranial sutures are not well established, particularly in a quantitative manner. Most prior work utilized planar reslicing approaches to analyze sutures and the quantitative measurements of suture morphometry were limited to a short segment not following the true skull shape. The present study aimed to investigate the age-based morphometric changes of the coronal suture during normal growth of young rats using a novel curved-reslicing approach.</div><div>Longitudinal in vivo micro-computed tomography (μCT) scans were completed at five time points (7, 9, 11, 16 and 21 weeks of age) during normal growth for 12 Sprague-Dawley rats (six female, six male). Curved-reslicing was performed on μCT slices to generate 11 equidistant cross-sectional images that covered the middle 90 % of skull thickness and the entire length of the coronal suture. The suture linear interdigitation index (LII) and width were measured using a marching algorithm.</div><div>The average coronal suture LII increased by 15.3 % while the width decreased by 53.5 % at 21 weeks compared to 7 weeks of age, and repeated measures one-way analysis of variance with post-hoc multiple comparisons with Bonferroni adjustment revealed that these differences are statistically significant (<em>p</em> &lt; 0.01). Linear mixed-effect models (LMM) were created for the prediction of rat coronal suture LII and width based on age, relative location through the skull thickness and initial morphometric measurements at the inner surface of the skull. When random effects are considered, the LMM was able to explain up to 97 % and 78 % of variations of suture LII and width, respectively. The presented study has established a novel curved-reslicing method to obtain quantitative 3D information surrounding cranial sutures and demonstrated strong predictive capabilities for suture morphometric changes with age. Future studies considering craniofacial sutures abnormalities will benefit from the presented work through novel methods of studying 3D quantitative morphometry.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"191 ","pages":"Article 117336"},"PeriodicalIF":3.5,"publicationDate":"2024-11-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142693991","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":"A NOTCH2 pathogenic variant and HES1 regulate osteoclastogenesis in induced pluripotent stem cells","authors":"Ernesto Canalis ,&nbsp;Lauren Schilling ,&nbsp;Emily Denker ,&nbsp;Christopher Stoddard ,&nbsp;Jungeun Yu","doi":"10.1016/j.bone.2024.117334","DOIUrl":"10.1016/j.bone.2024.117334","url":null,"abstract":"<div><div>Hajdu Cheney Syndrome (HCS), a monogenic disorder associated with <em>NOTCH2</em> pathogenic variants, presents with neurological, craniofacial and skeletal abnormalities. Mouse models of the disease exhibit osteopenia. To determine the consequences of a HCS pathogenic variant in human cells, induced pluripotent NCRM1 and NCRM5 stem (iPS) cells harboring a <em>NOTCH2</em>^{<em>6949C&gt;T</em>} mutation or null for <em>HES1</em> alleles were created. Parental iPSCs, <em>NOTCH2</em>^{<em>6949C&gt;T</em>}, <em>HES1</em> null and control cells, free of chromosomal aberrations were cultured under conditions of neural crest, mesenchymal and osteogenic cell differentiation, or of embryoid body, hematopoietic and osteoclast cell differentiation. The expected cell phenotype was confirmed by cell surface markers and gene signature. <em>NOTCH2</em>^{<em>6949C&gt;T</em>} cells displayed enhanced expression of Notch target genes demonstrating the presence of a NOTCH2 gain-of-function. There was a modest enhancement of osteogenesis in <em>NOTCH2</em>^{<em>6949C&gt;T</em>} cells manifested by increased mineralized nodule formation and <em>SP7</em>, <em>ALPL</em> and <em>BGLAP</em> mRNA expression. There was enhanced osteoclastogenesis in <em>NOTCH2</em>^{<em>6949C&gt;T</em>} cells as evidenced by increased number of osteoclasts and a transient increase in <em>ACP5</em>, <em>CALCR</em> and <em>CTSK</em> transcripts. Osteoblastogenesis was minimally affected by the <em>HES1</em> deletion, but osteoclast differentiation was significantly impaired. In conclusion, a <em>NOTCH2</em> pathogenic variant causes modest increases in osteoblastogenesis and osteoclastogenesis and HES1 is required for osteoclast differentiation in human iPS cells <em>in vitro</em>.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"191 ","pages":"Article 117334"},"PeriodicalIF":3.5,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142690081","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The functions and clinical implications of hsa_circ_0032462-miR-488-3p-SLC7A1 axis in human osteosarcoma","authors":"Ziyi Wang ,&nbsp;Zhenyuan Gao ,&nbsp;Yi-fei Yang ,&nbsp;Bi Liu ,&nbsp;Fei Yu ,&nbsp;Hai-ming Ye ,&nbsp;Ming Lei ,&nbsp;Xiaoming Wu","doi":"10.1016/j.bone.2024.117333","DOIUrl":"10.1016/j.bone.2024.117333","url":null,"abstract":"<div><h3>Background</h3><div>Osteosarcoma, as the most common primary malignant bone tumor, has become one of the main causes of cancer-related deaths in adolescents and children. This study thus proposes new biomarkers for OS based on whole-transcriptome re-analysis and experimental confirmation.</div></div><div><h3>Methods</h3><div>We find two circRNA dataset related to OS, from tissue and cell perspectives respectively, from the GEO database. Analysis of the tumor group and control group data used GEO2R, to obtain the differentially expressed (DE) circRNAs and take the intersection. The downstream miRNAs were predicted and subsequently the targeted mRNAs for these miRNAs were collected. These targeted mRNAs intersected with prognostic mRNAs reported in previous literature. CircRNA/miRNA/mRNA and circRNA/miRNA/mRNA/key pathway networks were constructed and GO and KEGG analyses were done. The prognostic values of hsa_circ_0032462, miR-488-3p, and SLC7A were confirmed in OS using Kaplan-Meier analyses and univariate/multivariate analyses. And the cellular functions of these three factors in OS were further explored through cell experiments.</div></div><div><h3>Results</h3><div>Five DEcircRNAs were obtained, targeting 42 miRNAs and linking 67 prognostic-related mRNA. GO analysis and KEGG analysis indicate that the mRNAs in the network were involved in various biological processes and signaling pathways related to OS. The luciferase report validated the targeting relationship of hsa_circ_0032462, miR-488-3p, and SLC7A. Cell survival, migration, and invasion experiments found that hsa_circ_0032462 and SLC7A promoted OS, while miR-488-3p inhibited OS.</div></div><div><h3>Conclusion</h3><div>Aberrantly expressed circRNAs in OS are involved in OS progression via the ceRNA network. Hsa_circ_0032462-miR-488-3p-SLC7A1 axis can be developed to be alternative therapeutic targets for OS.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"191 ","pages":"Article 117333"},"PeriodicalIF":3.5,"publicationDate":"2024-11-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142683871","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Effects of aging and exercise training on bone and marrow blood flow and vascular function","authors":"Hyerim Park ,&nbsp;S. Anand Narayanan ,&nbsp;Jacob T. Caldwell ,&nbsp;Bradley J. Behnke ,&nbsp;Judy M. Muller-Delp ,&nbsp;Michael D. Delp","doi":"10.1016/j.bone.2024.117335","DOIUrl":"10.1016/j.bone.2024.117335","url":null,"abstract":"<div><div>Aging leads to progressive bone loss, which is associated with impaired bone and marrow perfusion. The purpose of this study was to determine whether chronic exercise training enhances blood flow to the femur at rest and during exercise, and elucidate whether putative changes in training-induced bone perfusion are associated with alterations in the intrinsic vasomotor properties of the femoral principal nutrient artery (PNA) in old age.</div><div>Young (4–6 mo old) and old (20–22 mo old) male Fischer-344 rats were either treadmill exercise trained (ET) or remained sedentary (SED). Regional blood flow to the femur was assessed at rest and during treadmill exercise. Endothelium-dependent (acetylcholine, ACh) and -independent (Dea-NONOate) vasodilator, and vasoconstrictor (phenylephrine (PE), KCl and myogenic) responses of femoral PNAs were determined.</div><div>Exercise training led to higher blood flow to distal metaphysis and epiphysis in old rats at rest, and old ET rats showed greater regional blood flow during exercise compared to old SED rats. The increased blood flow to the proximal and distal metaphysis and epiphysis were also higher in old ET rats than that in young ET rats. Exercise training enhanced the vasodilator response to ACh, corresponding to increased eNOS expression in femoral PNAs from both young and old rats. Aging did not alter PE- or KCl-induced vasoconstriction, whereas myogenic responses were impaired. Exercise training enhanced vasoconstrictor responses to PE in old rats but had no effect on KCl or myogenic responses in either group.</div><div>These data demonstrate that exercise training enhances both regional bone and marrow blood flow and vasodilator responses, which are impaired in the femora of old SED rats.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"192 ","pages":"Article 117335"},"PeriodicalIF":3.5,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142677737","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Temporal trends in the burden of musculoskeletal diseases in China from 1990 to 2021 and predictions for 2021 to 2030","authors":"Yunfa Wang ,&nbsp;Bofan Chen ,&nbsp;Xinyue Liu ,&nbsp;Haimin Zeng ,&nbsp;Bin Chen ,&nbsp;Zhilin Wang ,&nbsp;Qingpiao Yang ,&nbsp;Jie Peng ,&nbsp;Liang Hao","doi":"10.1016/j.bone.2024.117332","DOIUrl":"10.1016/j.bone.2024.117332","url":null,"abstract":"<div><h3>Background</h3><div>Musculoskeletal (MSK) diseases represent a significant global public health challenge. Conducting comprehensive research on MSK diseases in China holds profound implications for public health.</div></div><div><h3>Methods</h3><div>This study utilized data from the Global Burden of Disease 2021 (GBD 2021) to analyze the incidence rate, prevalence rate, mortality rate, disability-adjusted life years (DALYs), years lived with disability (YLDs), and years of life lost (YLLs) of MSK diseases in China from 1990 to 2021. Trends were evaluated using annual percentage change (APC), average annual percentage change (AAPC), and estimated annual percentage change (EAPC). Future disease trends were predicted using the Bayesian Age-Period-Cohort (BAPC) model.</div></div><div><h3>Results</h3><div>China had the highest number of DALYs cases globally, totaling 30.4194 million. Low back pain (LBP) represented the largest burden, while hand osteoarthritis exhibited the fastest growth. Differences in disease burden were observed across various genders and age groups. Predictions indicate that between 2021 and 2030, the age-standardized DALYs rate in China will increase annually, reaching 1779.08 per 100,000 population by 2030. Environmental (occupational) factors had the most significant impact on the age-standardized DALYs rate, whereas renal dysfunction had the least impact. The SDI showed a moderately strong positive correlation with the age-standardized DALYs rate of MSK diseases.</div></div><div><h3>Conclusion</h3><div>Over the past 20 years, the prevalence of MSK diseases in China has experienced a slight increase, while other epidemiological burden indicators have shown a downward trend. Projections indicate that the overall disease burden of MSK in China will continue to rise over the next decade, underscoring the need for early intervention strategies. Moreover, substantial differences in MSK disease burden across genders and age groups highlight the importance of developing targeted policy interventions to mitigate this burden.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"191 ","pages":"Article 117332"},"PeriodicalIF":3.5,"publicationDate":"2024-11-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142650036","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Macrophage migration inhibitory factor promotes heterotopic ossification by mediating ROS/HIF-1α positive feedback loop and activating Wnt/β-catenin signaling pathway","authors":"Ping Li ,&nbsp;Wensheng Zhang ,&nbsp;Jie Zhang ,&nbsp;Jie Liu ,&nbsp;Jiaming Fu ,&nbsp;Zhengnong Wei ,&nbsp;Shiyong Le ,&nbsp;Jiajia Xu ,&nbsp;Liang Wang ,&nbsp;Zhongmin Zhang","doi":"10.1016/j.bone.2024.117331","DOIUrl":"10.1016/j.bone.2024.117331","url":null,"abstract":"<div><h3>Background</h3><div>Heterotopic ossification (HO) refers to the development of bone tissue in areas other than the skeletal system. The development and maturation of the skeletal system are significantly influenced by macrophage migration inhibitory factor (MIF). The objective of this study was to examine the impact of MIF on the in vitro osteogenic differentiation and mineralization of tendon-derived stem cells (TDSCs), mediated by a positive feedback loop involving ROS/HIF-1α/MIF.</div></div><div><h3>Methods</h3><div>TDSCs were isolated and identified from the hind limbs of C57/BL6 mice. The functional and procedural roles of MIF in HO, focusing on the impact of MIF on the differentiation of TDSCs into bone-forming cells were investigated in vitro. Seventy-five mice were randomly assigned to five groups. Gene expression and histological analyses of MIF and its receptors, and determine the expression of osteogenic markers in vivo.</div></div><div><h3>Results</h3><div>The results revealed a positive and concentration-dependent effect of MIF on the osteogenic differentiation of TDSCs. Furthermore, an ROS/HIF-1α/MIF positive loop was detected in the simulated early trauma hypoxic microenvironment, resulting in a 3 to 4 folds increase in MIF expression levels. MIF was also found to enhance double the expression levels of markers associated with bone and cartilage at the site of injury, consequently facilitating the development of HO, which was thought to be associated with the activation of the Wnt/β-catenin pathway.</div></div><div><h3>Conclusion</h3><div>MIF, which mediates the ROS/HIF-1α/MIF positive feedback loop during the hypoxic phase of HO, triggers the Wnt/β-catenin signaling pathway to enhance the osteogenic differentiation and formation of HO in TDSCs.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"190 ","pages":"Article 117331"},"PeriodicalIF":3.5,"publicationDate":"2024-11-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142645329","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}