Bone最新文献

{"title":"Response to ‘reconsidering bone-muscle interactions in obese older adults with type 2 diabetes: Methodological limitations and future directions’","authors":"Costas Glavas , Jakub Mesinovic , Peter R. Ebeling , Surbhi Sood , Elena S. George , Melkamu Tamir Hunegnaw , Ayse Zengin , Robin M. Daly , Paul Jansons , David Scott","doi":"10.1016/j.bone.2025.117700","DOIUrl":"10.1016/j.bone.2025.117700","url":null,"abstract":"","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117700"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145460842","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":"Inosine ameliorated bone destruction and inflammation in rheumatoid arthritis via inhibiting osteclastogenesis and synovial fibroblasts activation","authors":"Xia-nan Wu ,&nbsp;Ke Dong ,&nbsp;Li Liu ,&nbsp;Fang Lin ,&nbsp;Xi Wang ,&nbsp;Zhao-wei Gao ,&nbsp;Xiao-ming Zhu","doi":"10.1016/j.bone.2025.117734","DOIUrl":"10.1016/j.bone.2025.117734","url":null,"abstract":"<div><div>This study aim to investigate the effects of inosine on rheumatoid arthritis (RA) disease and explore the potential mechanism. Collagen-Induced Arthritis (CIA) rats were used to investigate the effects of inosine on bone destruction and inflammation. Micro-CT scan was used to detect the bone injury. H&amp;E and Safranin O staining were used to evaluate the synovial inflammation and cartilage damage. RANKL-induced osteoclasts differentiation assay was used to investigate the effects of inosine on osteclastogenesis. CCK-8 and transwell experiments were performed to investigate the RA synovioblast (RASFs) proliferation and invasion. We observed that inosine intraperitoneal injection led to significant reduction in arthritis score of CIA rats. Micro-CT scan showed the decreased degree of bone destruction and increased bone mass in inosine treated CIA-rats. H&amp;E and Safranin O staining showed that inosine significantly inhibited the inflammation and cartilage erosion in CIA-rats. The IL-6 and IL-8 levels in synovial tissues were lower in inosine treated CIA-rats than that in vehicle group. Furthermore, TRAP staining showed that the osteoclasts numbers were decreased in inosine treated CIA-rats. In vitro, inosine led to the decrease of osteoclasts numbers, F-actin ring and the expression of osteoclasts-specific markers. Furthermore, we found that inosine inhibited osteoclastogenesis via down-regulating OPN. OPN supplementation could counteract the inhibiting effect of inosine on osteoclastogenesis. Additionally, we observed that inosine significantly inhibited proliferation, invasion and inflammatory cytokines secretion of RASFs. In conclusion, inosine alleviated bone destruction and inflammation in CIA-rats by inhibiting osteoclastogenesis and RASFs activation. Hence, inosine supplementation may be a potential strategy for RA therapy.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117734"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145620923","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":"Loss of Tsc1 in Osterix-expressing cells leads to greater bone mass and strength in mice","authors":"Han Kyoung Choi ,&nbsp;Thomas Kim ,&nbsp;Xiaoxi Wei ,&nbsp;Karl J. Jepsen ,&nbsp;Yuji Mishina ,&nbsp;Nicholas Auyeung ,&nbsp;Fei Liu","doi":"10.1016/j.bone.2025.117695","DOIUrl":"10.1016/j.bone.2025.117695","url":null,"abstract":"<div><div>Tuberous sclerosis complex 1 (<em>Tsc1</em>) negatively regulates mTORC1 signaling, but its role in postnatal skeletal development is not fully understood. Previous studies using various Cre drivers to target osteoblasts or mesenchymal lineage cells have generally shown higher bone mass accompanied by disorganized bone structure. However, our earlier study using Osx-Cre-mediated <em>Tsc1</em> deletion demonstrated that conditional knockout mice (CKO) had lower femoral trabecular bone at one month of age, but early lethality prevented later-stage assessment. Furthermore, how postnatal mTOCRC1 hyperactivation affects bone accrual and mechanical properties remains unknown. In this report, we first evaluated the cortical bone phenotype of one-month-old CKO mice using nanoCT, immunostaining, and quantitative PCR (qPCR). CKO mice exhibited greater cortical bone mass, elevated osteoblast markers (<em>Alpl, Bsp, Col1a1, Ocn</em>) and transcription factors (<em>Runx2, Osx</em>), enhanced periosteal proliferation in vivo, and upregulated proliferation of primary femur cortical bone-derived osteoblasts in vitro. To overcome early lethality and assess the impact of postnatal mTORC1 hyperactivation, we utilized the built-in doxycycline (Dox) Turn-Off system in Osx-Cre mice to suppress Cre activity until 2 months of age. Postnatal <em>Tsc1</em> deletion from 2 to 5 months led to robust cortical and trabecular bone gains in the femur, calvariae, and vertebrae. Picrosirius Red staining demonstrated that the femoral cortical bone in CKO mice exhibited organized collagen with lamellar features, indicating preserved tissue quality. Importantly, four-point bending tests demonstrated significantly improved femoral mechanical strength in CKO mice. In summary, our data reveal differential effects of <em>Tsc1</em> deletion on trabecular and cortical bone at an early postnatal stage, and show that postnatal deletion results in robust bone gain with enhanced mechanical strength. These findings provide a more complete understanding of <em>Tsc1</em>-mTORC1 signaling as a key regulator of bone mass and challenge the assumption that mTORC1 hyperactivation yields mechanically inferior bone.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117695"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145427149","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":"Craniofacial fibrous dysplasia: Long-term postoperative outcomes in a retrospective case series with up to 40 years of follow-up","authors":"Pin-Ru Chen ,&nbsp;Kai-Ti Chuang ,&nbsp;Po-Fang Wang ,&nbsp;Chuan-Fong Yao ,&nbsp;Pang-Yun Chou ,&nbsp;Ying-An Chen ,&nbsp;Clement Cheng-Hui Lin ,&nbsp;Hong-Yuan Huang ,&nbsp;Yu-Ray Chen","doi":"10.1016/j.bone.2025.117697","DOIUrl":"10.1016/j.bone.2025.117697","url":null,"abstract":"<div><h3>Background</h3><div>Craniofacial fibrous dysplasia (CFD) is a non-malignant disease characterized by fibro-osseous lesions in the affected bones. Management is multidisciplinary, with surgery often serving as the mainstay of treatment and stratified according to four anatomical zones. This study aimed to evaluate the long-term outcomes and assess potential modifications to the algorithm.</div></div><div><h3>Methods</h3><div>This retrospective study included patients diagnosed with CFD or McCune–Albright syndrome (MAS) who received surgical intervention between 1972 and 2000, with a follow-up period exceeding 20 years. Demographic characteristics, surgical procedures, and follow-up computed tomographic scans and photographs were included in the analysis.</div></div><div><h3>Results</h3><div>Of 93 surgically treated patients with CFD/MAS, 13 were available for ≥20-year follow-up, with complete data and CT imaging (mean 30 ± 6 years, range 20–40 years). Ten patients underwent radical resection and immediate bone graft reconstruction, and two of them experienced recurrence. Three patients underwent therapeutic optic nerve decompression, and two patients experienced post-surgical vision improvement. One patient underwent surgery for hearing loss in the external auditory canal and experienced improved hearing post-surgery. One patient diagnosed with MAS experienced significant relief from craniofacial pain after receiving adjuvant hormone therapy.</div></div><div><h3>Conclusions</h3><div>Surgical strategies tailored to the four anatomical zones of CFD yield satisfactory outcomes. For Zone 1 lesions, based on our experience, radical resection followed by immediate bone graft reconstruction is a viable option. In Zone 3, therapeutic rather than prophylactic optic nerve decompression is suggested. Orthognathic surgery is also a viable option for such patients, improving occlusion and facial appearance.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117697"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145446881","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 C-type lectin receptor mincle is functionally expressed by murine bone cells and can mediate inflammatory osteoblast responses to Staphylococcus aureus","authors":"Erin L. Mills ,&nbsp;Quinton A. Krueger ,&nbsp;Aiza Noyal ,&nbsp;M. Brittany Johnson ,&nbsp;Ian Marriott","doi":"10.1016/j.bone.2025.117689","DOIUrl":"10.1016/j.bone.2025.117689","url":null,"abstract":"<div><div>It is now apparent that osteoblasts and osteoclasts have immune functions that play a critical role in shaping host responses and the abnormal bone remodeling associated with staphylococcal infections. Both cell types express various pattern recognition receptors (PRRs) that enable them to perceive pathogens and initiate the production of mediators that can exacerbate infection-induced inflammatory bone loss. Macrophage-inducible C-type lectin (Mincle) is a tyrosine activation motif–coupled PRR that can recognize glycolipids from diverse pathogens to initiate inflammatory mediator production. In the lung, an important role for Mincle has been suggested in host defense against Gram positive bacteria. In the present study, we report that RNA Tag-Seq analysis of <em>S. aureus</em> infected murine osteoclasts and osteoblasts revealed enrichment of genes associated with C-type lectin receptor-mediated responses and elevated expression of mRNA encoding Mincle and its key downstream signaling components. We have found robust levels of Mincle protein in murine osteoclasts and osteoblasts, and demonstrated the inducible expression of this molecule in primary human osteoblasts. The functional nature of Mincle expression by osteoclasts and osteoblasts was confirmed by the ability of Mincle-specific agonists to elicit inflammatory cytokine production by these cells. Importantly, we have shown that the cytokine responses of <em>S. aureus</em> challenged murine and human osteoblasts are attenuated following Mincle blockade. Together, these studies support the assertion that bone cells functionally express Mincle and that this C-type lectin can mediate, at least in part, the inflammatory immune responses of osteoblasts to <em>S. aureus</em> challenge.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117689"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145442607","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":"Author response to letter to the editor, “PINP-guided osteoporosis treatment selection: methodological considerations for cut-off, endpoint, fracture confounding and teriparatide heterogeneity”","authors":"Yuki Etani ,&nbsp;Takaaki Noguchi ,&nbsp;Toshitaka Yukishima ,&nbsp;Tomonori Kobayakawa ,&nbsp;Masafumi Kashii ,&nbsp;Gensuke Okamura ,&nbsp;Atsushi Goshima ,&nbsp;Makoto Hirao ,&nbsp;Taihei Miura ,&nbsp;Takuya Kurihara ,&nbsp;Yuji Fukuda ,&nbsp;Atsushi Sugimoto ,&nbsp;Seiji Okada ,&nbsp;Ken Nakata ,&nbsp;Kosuke Ebina","doi":"10.1016/j.bone.2025.117725","DOIUrl":"10.1016/j.bone.2025.117725","url":null,"abstract":"","PeriodicalId":9301,"journal":{"name":"Bone","volume":"203 ","pages":"Article 117725"},"PeriodicalIF":3.6,"publicationDate":"2026-02-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145524807","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":"Melatonin promotes osteogenic differentiation of BMSCs by regulating circZFAND1/miR-433-3p/DKK1 pathway through melatonin receptor-dependent m6A modification of circZFAND1","authors":"Yubo Shi ,&nbsp;Jianzhou Yu ,&nbsp;Yanqing Wu ,&nbsp;Hao Fang ,&nbsp;Bo Yang","doi":"10.1016/j.bone.2025.117691","DOIUrl":"10.1016/j.bone.2025.117691","url":null,"abstract":"<div><div>An effective approach for treating osteoporosis (OP) is to focus on restoring the osteogenic ability of bone marrow-derived mesenchymal stem cells (BMSCs). Melatonin (MEL) has been found to possess the capability to enhance osteogenesis. Nevertheless, the precise mechanisms through which MEL regulates the differentiation of BMSCs and the development of OP are still not well understood. In the present study, circZFAND1 characterization was validated using Sanger sequencing, RNase R treatment, and RNA fluorescence in situ hybridization assay. To investigate the relationship between circZFAND1, DKK1 and miR-433-3p, we performed a series of experiments including the luciferase reporter assay, RNA immunoprecipitation assay, and rescue experiments. In addition, the MEL-mediated m6A modification of circZFAND1 was evaluated using dot-blot assay and Methylated RNA immunoprecipitation (Me-RIP) assay. Finally, the osteogenic differentiation of BMSCs was detected through function assays, including immunofluorescence staining, 5-ethynyl-20-deoxyuridine (EdU) assay, western blotting, and staining with alkaline phosphatase and alizarin red. The results showed that MEL promoted osteogenic differentiation of BMSCs by regulating circZFAND1/miR-433-3p/DKK1 pathway through melatonin receptor 2 (MT2) -dependent m6A modification of circZFAND1. These findings offer novel biomarkers for managing OP and may lay the theoretical foundation for applying MEL for OP management in the clinical setting.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"202 ","pages":"Article 117691"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145454174","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":"Cathepsin K-lineage cells and mechanical loading independently modulate bone mass in the murine tibia","authors":"Tyler J. McNeill ,&nbsp;Seoyeon Bok ,&nbsp;Branden R. Sosa ,&nbsp;Michelle Cung ,&nbsp;Matthew B. Greenblatt ,&nbsp;Marjolein C.H. van der Meulen","doi":"10.1016/j.bone.2025.117693","DOIUrl":"10.1016/j.bone.2025.117693","url":null,"abstract":"<div><div>The ability of bone to adapt to external mechanical loads has been extensively studied, with mechanical stimuli increasing cortical and cancellous bone mass. However, the stem cell basis underlying this response is not well understood. To date, most studies focused on the role of differentiated cell populations in the skeletal response to loading. A recently discovered periosteal-specific skeletal stem cell marked by cathepsin K (CTSK) that drives intramembranous bone formation is a promising candidate to mediate load-induced bone formation. In this study, we sought to determine the influence of CTSK-lineage cells on the skeletal response to mechanical loading. We ablated cells expressing CTSK prior to initiating cyclic tibial compression for two weeks beginning at 16 weeks of age. We analyzed cortical and cancellous bone morphology at the tibial metaphysis and cortical bone morphology at the mid-diaphysis. Loading increased cortical, but not cancellous, bone mass. The amount of bone formed in response to loading did not differ when CTSK-expressing cells were ablated. CTSK-lineage cell ablation increased cortical bone mass primarily in regions subjected to tension and loading predominantly affected regions of bone under compression. To analyze the material composition of load-induced bone, we performed Raman spectroscopy along the periosteal surface of the diaphysis. CTSK-lineage cell ablation altered the influence of loading on B-type carbonate substation, a measure of tissue age. Overall, the amount of bone formed in response to loading did not differ in the absence of CTSK-lineage cells, but the material composition of load-induced cortical tissue was altered.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"202 ","pages":"Article 117693"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145423588","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":"Reconsidering bone–muscle interactions in obese older adults with type 2 diabetes: Methodological limitations and future directions","authors":"Shangxuan Li","doi":"10.1016/j.bone.2025.117699","DOIUrl":"10.1016/j.bone.2025.117699","url":null,"abstract":"","PeriodicalId":9301,"journal":{"name":"Bone","volume":"202 ","pages":"Article 117699"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145411061","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":"Enhancing Wnt signaling lowers fracture incidence in a severe mouse model of Osteogenesis Imperfecta","authors":"Giulia Montagna ,&nbsp;Stephanie Lee ,&nbsp;Austin Baacke ,&nbsp;Matthew L. Warman ,&nbsp;Christina M. Jacobsen","doi":"10.1016/j.bone.2025.117641","DOIUrl":"10.1016/j.bone.2025.117641","url":null,"abstract":"<div><div>Increased fracture is a hallmark feature of the skeletal disorder Osteogenesis Imperfecta (OI). A neutralizing antibody against sclerostin, an endogenous Wnt signaling inhibitor, has been FDA-approved for osteoporosis and is now in clinical trials for OI. This anti-sclerostin antibody increased bone mass and skeletal strength in several preclinical models of OI.</div><div>Because <em>in vivo</em> fracture incidence is the primary outcome measure in human OI clinical trials, we examined the effect of enhancing Wnt signaling in a preclinical mouse model of severe, autosomal dominant OI (the <em>Col1a1^Aga2/+</em> mouse). We genetically enhanced Wnt signaling using the <em>Lrp5^A214V</em> allele, which makes the Wnt co-receptor LRP5 resistant to sclerostin inhibition. By crossing <em>Col1a1^Aga2/+</em> sires with <em>Lrp5^A214V/+</em> dams, we generated pups with OI alone and pups with OI plus enhanced Wnt signaling. We radiographically examined these animals for fractures at 5, 9, and 13 weeks of age and also measured their mobility using a Holeboard assay.</div><div>We found that enhanced Wnt signaling significantly reduced fracture numbers in this OI model by 30 % at each age but did not significantly affect mobility. These data indicate that an enhanced Wnt signaling decreases fracture incidence in a preclinical model of severe OI and suggest that lower fracture rates could be achieved by administering anti-sclerostin antibodies to OI patients.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"202 ","pages":"Article 117641"},"PeriodicalIF":3.6,"publicationDate":"2026-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"145058838","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}