JBMR Plus最新文献

{"title":"Fecal microbiota transplantation in mice improves bone material properties through altered mineral quality.","authors":"Bowen Wang, Samuel J Stephen, Erika L Cyphert, Chongshan Liu, Christopher J Hernandez, Deepak Vashishth","doi":"10.1093/jbmrpl/ziaf115","DOIUrl":"10.1093/jbmrpl/ziaf115","url":null,"abstract":"<p><p>Disruptions of the composition of the gut microbiome are linked to impaired bone tissue strength. Fecal microbiota transplantation (FMT) is an established clinical therapy that can restore a healthy gut microbiome and reduce systemic inflammation. However, whether FMT from a healthy donor could rescue bone fragility is unknown. As induced inflammation causes mineralization defects, we hypothesize that manipulations of the gut microbiota alter bone fracture resilience through changes in mineral quality. Here, we altered the compositions of the gut microbiome in mice via antibiotics (ampicillin and neomycin) and FMT. Mice were allocated to 5 groups (M/F, <i>N</i> = 13-18/group): Unaltered, Continuous (dosed 4-24 wk), Initial (dosed 4-16 wk), Reconstituted (dosed 4-16 wk with subsequent FMT from age- and sex-matched mice with unaltered gut microbiota), and Delayed (dosed 16-24 wk). Fracture toughness testing and Raman spectroscopy were conducted on the femora. The maximum toughness was greater in the Reconstituted group (for females, <i>p</i> < .05 compared to Continuous, Unaltered, and Delayed groups; for males, <i>p</i> < .05 compared to groups with antibiotic dosing). The Reconstituted group showed lower type-B carbonate substitution in the bone mineral (all <i>p</i> < .01 for both sexes), and lower mineral-to-matrix ratio (all <i>p</i> < .01 for males, for females, <i>p</i> < .01 compared to Unaltered, Initial, and Delayed groups). In females, mineral crystallinity was higher in the Reconstituted group than those dosed with antibiotics (all <i>p</i> < .05). Serum inflammation marker TNF-α was positively correlated with type-B carbonate substitutions (ρ = 0.66), mineral-to-matrix ratio (ρ = 0.71), and carboxymethyl-lysine (CML) in bone matrix (ρ = 0.43). Enhanced bone maximum fracture toughness was associated with reduced type-B carbonate substitution (<i>r</i> = -0.45), decreased mineral-to-matrix ratio (<i>r</i> = -0.40), increased mineral crystallinity (<i>r</i> = 0.33), and lower levels of bone CML (<i>r</i> = -0.49, all <i>p</i> < .01). These results suggest that the introduction of more beneficial gut microbiota can increase fracture resistance by modifying mineral composition and quality, likely through the reduction of systemic inflammation.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 9","pages":"ziaf115"},"PeriodicalIF":2.4,"publicationDate":"2025-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12374538/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954045","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Combined antiresorptive and new anabolic drug approach in osteogenesis imperfecta zebrafish models.","authors":"Cecilia Masiero, Francesca Tonelli, Carla Aresi, Marta Filibian, Daria Larionova, Silvia Cotti, Filippo Doria, Camilla Torriani, Paola Bertuccio, Anna Odone, Simona Villani, Antonio Rossi, Paul Eckhard Witten, Antonella Forlino","doi":"10.1093/jbmrpl/ziaf112","DOIUrl":"10.1093/jbmrpl/ziaf112","url":null,"abstract":"<p><p>Osteogenesis imperfecta (OI) is a family of heritable collagen I-related skeletal disorders for which, to date, no definitive cure is available. Individuals with OI are mainly treated with bisphosphonates that enhance bone mass by inhibiting bone resorption. However, new strategies combining antiresorptive molecules with bone anabolic drugs are likely to provide valid alternatives for skeletal health, protecting physiological bone turnover. Recently, cellular stress has been identified as a therapeutic target in both dominant and recessive forms of OI characterized by overmodified collagen I. The chemical chaperone 4-phenylbutyrate (4PBA) successfully ameliorated cell homeostasis in both in vitro and in vivo OI models. In this study, dominant <i>Chihuahua</i> (<i>Chi/+</i>) and recessive <i>p3h1^-/-</i> zebrafish OI models were treated for 2 mo either with the bisphosphonate alendronate (ALN) or with 4PBA or with a combination of the two. The treatment effect at the tissue level was evaluated by microCT analysis of the vertebral body, while histology and gene expression analyses allowed to dissect the consequences at a cellular level. Only ALN administration improved the vertebral thickness in the dominant <i>Chi/+</i> model. The combined therapy synergistically improved osteoblast homeostasis and promoted the formation of mature extracellular collagen fibers in both models. All treatment conditions reduced osteoclast TRAP activity in <i>Chi/+</i>, whereas 4PBA and 4PBA + ALN had the opposite effect on <i>p3h1^-/-</i> . Finally, 4PBA and the combination of ALN and 4PBA reduced osteocyte apoptosis only in <i>p3h1^-/-</i> . Our data demonstrated for the first time in vivo a differential effect of the combination of an antiresorptive and a new anabolic compound in dominant and recessive OI zebrafish models, stressing the importance of identifying the specific causative molecular defect to define the best treatment option.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 9","pages":"ziaf112"},"PeriodicalIF":2.4,"publicationDate":"2025-07-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12356371/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873177","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessment, diagnostic criteria, and outcome measures for non-femoral head lower limb avascular necrosis in children and adolescents: a scoping review.","authors":"Rhianydd Thomas, Stephanie Ball, Luke Davies, Nicole Williams, Cylie Williams, Craig Munns, Verity Pacey","doi":"10.1093/jbmrpl/ziaf109","DOIUrl":"10.1093/jbmrpl/ziaf109","url":null,"abstract":"<p><p>Avascular necrosis is a condition that results from disruption of the blood supply to bone. It can develop idiopathically or secondary to disease or corticosteroid use. To facilitate consistent clinical and research practice, this review aimed to identify methods used to assess, diagnose, and determine outcomes of non-femoral head (non-FH) lower limb avascular necrosis in children and adolescents. We conducted a scoping review up to January 2024, searching Ovid Medline, Embase, CINAHL, and Scopus databases. Studies were included if they had 10 or more individuals aged 0-17 yr with non-FH lower limb avascular necrosis, and included assessment, diagnostic criteria, or outcome measures. Measures identified were grouped according to the International Classification of Functioning, Disability, and Health framework of impairments of body function and structure, activity limitations, and participation restrictions. Following full-text screening, 31 studies met the inclusion criteria: 24 of these studies were retrospective (77%). Twenty-three studies involved secondary avascular necrosis (74%) and 8 studies involved primary avascular necrosis (26%). MRI and radiographs were most frequently used for diagnosis. Impairments were predominantly assessed via patient report, and use of validated measures was limited. There was also limited consideration of activity limitations and participation restrictions in both assessment and outcome measures. Where present, these were patient reported. The findings highlight a strong focus on impairments despite a need to consider the conditions impact on activity limitations and participation restrictions. Obtaining consensus on assessments and outcome measures, with increased use of validated measures to improve rigor, would facilitate collation of results in future research.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 9","pages":"ziaf109"},"PeriodicalIF":2.4,"publicationDate":"2025-06-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12356369/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144873176","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Ectopic pseudojoints in fibrodysplasia ossificans progressiva.","authors":"Robert J Pignolo, Mona Al Mukaddam, Stephen Broski, Rolf Morhart, Luke T Drake, Bruce Kneeland, O Will Towler, Frederick S Kaplan","doi":"10.1093/jbmrpl/ziaf107","DOIUrl":"10.1093/jbmrpl/ziaf107","url":null,"abstract":"<p><p>Pseudoarthroses (false joints) occur as a complication of fracture healing in the normotopic skeleton but have not been reported at ectopic sites. Fibrodysplasia ossificans progressiva (FOP) is an ultra-rare genetic disorder characterized by progressive heterotopic ossification (HO) and congenital skeletal abnormalities including developmental arthropathy in the normotopic skeleton. Here, we report ectopic pseudojoint formation in 6 patients with FOP, all occurring after painful flare-ups and HO in soft connective tissues of the knee, hip, and forearm. To our knowledge, FOP is the only human condition in which ectopic pseudojoint formation occurs. These findings support that dysregulated BMP pathway signaling from mutant ACVR1 mediates not only HO, but also ectopic pseudojoint formation, and that ectopic pseudojoints can arise from de novo musculoskeletal elements.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 8","pages":"ziaf107"},"PeriodicalIF":2.4,"publicationDate":"2025-06-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12315676/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144775405","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"High-resolution peripheral quantitative computed tomography reliability and accuracy of bone density and morphology properties in children.","authors":"Roman J Shypailo, Chadi Calarge, Punam K Saha, Xiaoliu Zhang, Xiaojie Chen, Stephanie Dinh, Xiaofan Huang, Babette S Zemel, Fida Bacha","doi":"10.1093/jbmrpl/ziaf106","DOIUrl":"10.1093/jbmrpl/ziaf106","url":null,"abstract":"<p><p>Volumetric bone density, microarchitecture, and strength measures using HR-pQCT are valuable measures of bone health in pediatrics. Our cross-sectional study evaluated bone measure reproducibility in pediatric participants using repeat HR-pQCT (XtremeCT II, Scanco Medical) scans of non-dominant distal tibia and radius of 30 healthy children and adolescents (7-17 yr, 47% female) by 2 technicians. Additionally, we examined HR-pQCT and micro-CT of 26 cadaveric distal tibia specimens to evaluate agreement between the modalities. All HR-pQCT scans were analyzed using manufacturer-provided software (Image Processing Language, Scanco Medical) and a fully automated, previously validated, in-house algorithm, offering measures of bone microstructure (eg, trabecular plate-rod distribution, transverse trabeculae, trabecular bone strength) currently unavailable in the manufacturer-provided software. Root-mean-squared percent coefficient of variation (RMS-%CV) assessed precision and least significant change. Intraclass correlation coefficients (ICCs) using absolute-agreement, 2-way random-effects models assessed reliability. Pearson's correlation coefficients and ICC assessed linear relationships and agreements between HR-pQCT and micro-CT, respectively. In children and adolescents, RMS-%CV of HR-pQCT-derived trabecular bone measures at distal tibia and radius ranged from 0.8-4.4 to 0.8-6.0, respectively. Most cortical bone results were in a similar range. Both computational algorithms showed ICC > 0.90. RMS-%CV and least significant change values were lower for tibia than radius. ICCs were lower for cortical than trabecular outcomes. Most cadaveric results showed ICC > 0.83, other than trabecular bone thickness and modulus (ICC = 0.7). Pearson's <i>r</i> (>0.86) suggested strong correlations for almost all parameters. HR-pQCT and micro-CT results using in-house algorithm did not differ significantly, while manufacturer-provided algorithm results showed lower yet still moderate reliability (ICC > 0.55). Reliability of the second-generation HR-pQCT in pediatric participants is excellent-better in tibia vs radius. Our results support the high reproducibility of XtremeCT II scans and thus the use of this clinical imaging modality in studies of pediatric bone health.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 9","pages":"ziaf106"},"PeriodicalIF":2.4,"publicationDate":"2025-06-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12395334/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144954295","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Direct and indirect effects of transforming growth factor-beta on osteoclast-mediated bone remodeling using a new in vitro bone matrix model.","authors":"Risako Chiba-Ohkuma, Takeo Karakida, Ryuji Yamamoto, Yasuo Yamakoshi","doi":"10.1093/jbmrpl/ziaf104","DOIUrl":"10.1093/jbmrpl/ziaf104","url":null,"abstract":"<p><p>Transforming growth factor-beta (TGF-β), a cytokine embedded in the bone matrix, is released during bone resorption, influencing osteoclast differentiation and coupling factor production, which affect osteoblasts and osteocytes. This study investigates the role of TGF-β in bone remodeling using an in vitro model with calcium phosphate-coated plates covalently bonded to latent TGF-β (LTGF-β(+)-CaP plates). This model replicates the natural release of TGF-β and its effects on RAW264 macrophage-like cells, which differentiate into osteoclasts upon stimulation of RANKL. Cells cultured on LTGF-β(+)-CaP plates formed resorption pits and released TGF-β, upregulating osteoclast differentiation- and resorption-related genes during early differentiation. During the resorption phase, TGF-β-enhanced osteoblast activation and coupling factor expression supporting bone formation in surrounding cells. In osteocytes, it differentially regulated gene expression by upregulating osteoprotegerin and downregulating sclerostin, suggesting a dual role in remodeling. Our findings demonstrate that TGF-β plays a critical role in bone homeostasis by directly promoting osteoclast differentiation and resorption while indirectly facilitating osteoblast differentiation through coupling factors. These results provide insights into the dynamic interactions between osteoclasts, osteoblasts, and osteocytes, emphasizing TGF-β's role in linking bone resorption and formation. This study establishes a novel in vitro platform to examine TGF-β-mediated bone remodeling and its underlying molecular mechanisms. Furthermore, our model can be used to explore how TGF-β signaling affects cellular communication in the bone and may contribute to identifying new therapeutic targets for osteoporosis and other bone-resorptive disorders.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 8","pages":"ziaf104"},"PeriodicalIF":2.4,"publicationDate":"2025-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12306438/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144742107","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Longitudinal patient outcomes over 18 months following a hip, clinical vertebral, distal forearm, or proximal humerus fracture in the United States: results from the ICUROS US study.","authors":"Stuart Silverman, Deborah Gold, Michael Nichol, John Schousboe, Rebecca Smith, Anna Tosteson","doi":"10.1093/jbmrpl/ziaf077","DOIUrl":"10.1093/jbmrpl/ziaf077","url":null,"abstract":"<p><p>The longitudinal impact of fractures associated with osteoporosis on costs and health-related quality of life is not well understood. The objective of this study was to characterize these outcomes over an 18-mo period following 4 common fracture types. Patients aged over 50 yr at 7 study sites with a diagnosis of incident hip, distal radius, proximal humerus, or vertebral fracture were enrolled in the International Costs and Utilities Related to Osteoporotic Fracture Study US. Data collection by questionnaire occurred at baseline (within 6 wk of fracture), 4-, 12-, and 18-mo post-fracture. Direct, indirect, and total costs were estimated over an 18-mo period and are reported in 2020 US Dollars. Health utilities were measured using EuroQol EQ-5D and the SF-6D. We performed longitudinal regression models of estimated costs adjusted for age and sex. We enrolled 284 patients with single fragility fractures (58 hip, 50 distal radius, 32 proximal humerus, 144 vertebral). Mean ages were 68.1 yr for distal radius and proximal humerus and 76 yr for hip patients. Most participants were women (76%-84% women). Over the 18-mo study period, direct costs (Including initial fracture and fracture related follow-up costs) were $18 495 for hip, $3451 for distal forearm, $6009 for humerus, and $9274 for vertebral fracture. Mean indirect costs were $9250 for hip, $1772 for distal radius, $4195 for humerus, and $4084 for vertebral fracture. Adjusted mean EQ-5D differences (95% CI) at 18-mo for those surviving/reporting compared with baseline were: hip -0.162 (95% CI, -0.22 to -0.103), distal radius -0.017 (95% CI, -0.056 to 0.022), proximal humerus -0.064 (95% CI, -0.103 to -0.0248), and vertebral -0.044 (95% CI, -0.083 to -0.0048). Substantial direct and indirect costs are observed in the 18-mo following 4 common osteoporotic fractures. Significant changes in health utility persisted for all fractures other than distal radius fractures regardless of the health utility measure used.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 7","pages":"ziaf077"},"PeriodicalIF":3.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12203106/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528004","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction to: Fracture discrimination capability of ulnar flexural rigidity measured via Cortical Bone Mechanics Technology: study protocol for The STRONGER Study.","authors":"","doi":"10.1093/jbmrpl/ziaf095","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziaf095","url":null,"abstract":"<p><p>[This corrects the article DOI: 10.1093/jbmrpl/ziad002.].</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 6","pages":"ziaf095"},"PeriodicalIF":3.4,"publicationDate":"2025-05-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12123522/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144199146","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Bone phenotype in male and female mice after knockdown of transferrin receptor 1 in osterix-expressing cells.","authors":"Vanessa Passin, Maria G Ledesma-Colunga, Ulrike Baschant, Lorenz C Hofbauer, Martina Rauner","doi":"10.1093/jbmrpl/ziaf069","DOIUrl":"10.1093/jbmrpl/ziaf069","url":null,"abstract":"<p><p>Transferrin receptor 1 (Tfr1) plays a key role in mediating the cellular uptake of transferrin-bound iron. While Tfr1 is essential for iron uptake in erythroid cells and skeletal muscle, it is dispensable for iron acquisition in hepatocytes, intestinal epithelial, or endothelial cells. In this study, we investigated the significance of Tfr1 for iron uptake and cellular function in bone-forming osteoblasts. Therefore, we examined the bone characteristics of male and female Tfr1^fl/fl;Osx:cre^+/- (osteoprogenitors) conditional KO mice at 12 and 24 wk of age. Bone marrow-derived cells from Tfr1^fl/fl;Osx:cre^+/- mice were differentiated into osteoblasts in vitro to assess cellular iron status as well as cellular differentiation and function. Our findings indicate that Tfr1 deficiency in osteoprogenitors in male mice resulted in increased trabecular bone mass in the axial skeleton with decreased bone formation rate as well as decreased levels of serum bone turnover markers. Despite increased bone mass in the femur in females resulting from Tfr1 deficiency in osteoprogenitors, loss of bone mass following ovariectomy was not mitigated. Transferrin receptor 1-deficient osteoblasts showed mild changes in cytosolic iron levels and decreased mineralization. These results suggest a minor role of Tfr1 in osteoblasts differentiation and function but highlight distinct strategies for iron acquisition employed by bone cells to maintain cellular iron homeostasis.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 7","pages":"ziaf069"},"PeriodicalIF":3.4,"publicationDate":"2025-05-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12145871/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144247908","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Sirtuin-3 promotes osteoclast maturation and bone loss by regulating mitochondrial ROS production during ionizing radiation exposure.","authors":"Gareeballah Osman Adam, Kimberly K Richardson, Ankita Chalke, Qiang Fu, Jeff D Thostenson, Hutomo Tanoto, Yuxiao Zhou, Nukhet Aykin-Burns, Ha-Neui Kim","doi":"10.1093/jbmrpl/ziaf092","DOIUrl":"10.1093/jbmrpl/ziaf092","url":null,"abstract":"<p><p>Ionizing radiation (IR) exposure leads to mitochondrial alterations in osteoclasts and osteoblasts, contributing to musculoskeletal disintegration. Despite this, the mechanisms controlling mitochondrial activity in bone cells during IR exposure-associated bone disorders remain underexplored. Sirtuin-3 (SIRT3), a NAD-dependent mitochondrial deacetylase, is essential for the enhanced mitochondrial function in osteoclasts and the increased bone resorption observed in osteoporosis. However, it is still unclear whether and how SIRT3 drives IR exposure-induced bone disorders. Here, we show that deletion of <i>Sirt3</i> greatly attenuated the IR exposure-induced loss of bone mass in young adult mice. This effect was associated with impaired osteoclast maturation and function, thus suppressing excessive bone resorption. IR exposure also increased mitochondrial activity and ROS production in osteoclasts. Deletion of <i>Sirt3</i> abrogated these effects of IR exposure. The levels of mitochondrial superoxide dismutase 2 (SOD2), a major component of the metabolic machinery that handles ROS in the mitochondrial matrix, were significantly increased in osteoclasts by RANKL with an identical pattern as SIRT3. Deacetylation of lysine 68 of SOD2 enhanced the formation of giant osteoclasts and increased mitochondrial ROS production, mimicking the effects of IR exposure. Inhibition of mitochondrial ROS production via Mito-TEMPO recapitulated the effects of <i>Sirt3</i> deletion on osteoclast maturation and mitochondrial activity during IR exposure. These findings demonstrate that SIRT3 plays an essential role in IR exposure-induced bone resorption by promoting deacetylation in osteoclast mitochondria. Understanding the mechanisms of mitochondrial quality control and protein acetylation in osteoclasts could pave the way for developing novel strategies to counteract IR exposure-associated bone disorders.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"9 7","pages":"ziaf092"},"PeriodicalIF":3.4,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12202156/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144528006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}