JBMR Plus最新文献

{"title":"New knock-in mouse lines <i>Dmp1^em1(CreERT2)</i> and <i>Dmp1^em2(ZsGreen)</i> enable precise osteocyte-specific targeting and visualization.","authors":"Yizhong Jenny Hu, Yvonne Qianqin Guo, Ting Hsuan Wang, Manyun Yang, Yuchen Liu, Yingzi Yang","doi":"10.1093/jbmrpl/ziag031","DOIUrl":"10.1093/jbmrpl/ziag031","url":null,"abstract":"<p><p>Bone in adult mammals plays critical structural and endocrine functions, both largely rely on osteocytes-the most abundant bone cells and principal source of bone-derived hormones, such as fibroblast growth factor 23 and sclerostin. The widely used 10-kb promoter-driven transgenic <i>Tg(Dmp1-Cre)</i> and <i>Tg(Dmp1-CreERT2)</i> lines, while widely used and helpful, utilize transgenic approaches with transgene expression driven by the <i>Dmp1</i> promoter. The transgene expression suffers from positional effects with off-target expression in muscle, brain, and other tissues, limiting their applications, causing a major technical gap in the investigation of osteocyte-specific functions. Here, we generated 2 novel mouse lines-<i>Dmp1^em1(CreERT2)</i> and <i>Dmp1^em2(ZsGreen)</i> -via CRISPR-Cas9 mediated \"knock-in\" approaches to insert an internal ribosome entry site (<i>IRES</i>)<i>-CreERT2</i> or <i>IRES-ZsGreen</i> cassette into the <i>Dmp1</i> locus, allowing <i>CreER^T2</i> or <i>ZsGreen</i> expression under the genetic control of the endogenous <i>Dmp1</i> locus while preserving <i>Dmp1</i> gene expression. We show that the <i>Dmp1^em1(CreERT2)</i> enabled highly efficient tamoxifen-inducible recombination (>90% in cortical and trabecular osteocytes) with minimal off-target expression in non-bone tissues. The <i>Dmp1^em2(ZsGreen)</i> line showed robust, fixation-, and decalcification-resistant green fluorescence in osteocytes from birth through adulthood, faithfully reflecting endogenous <i>Dmp1</i> expression. Lineage tracing using the <i>Dmp1^em1(CreERT2)</i> line further revealed that the cortical osteocytes are long-lived, whereas trabecular osteocytes undergo continuous renewal, uncovering compartment-specific differences in osteocyte lifespan. By eliminating off-target recombination or gene expression in skeletal muscle, brain, gastrointestinal tract, and marrow compartments, the 2 mouse lines offer powerful tools for rigorous studies in osteocyte biology, mechanotransduction, and bone regulation of systemic physiology that impact health, aging, and diseases, while minimizing complications due to off-target transgene expression.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 4","pages":"ziag031"},"PeriodicalIF":3.0,"publicationDate":"2026-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13007860/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147512188","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":"Impaired bone matrix turnover with selective small bone fragility in a child with <i>TENT5A</i>-associated osteogenesis imperfecta.","authors":"Alex Guo, Cara Tillotson, Cecilia Sena, Adhirai Muthukumar, Madhulatha Pantrangi, Mythily Ganapathi, Olga Gewartowska, Paweł S Krawczyk, Vidhu V Thaker, Ekaterina Semenova","doi":"10.1093/jbmrpl/ziag029","DOIUrl":"10.1093/jbmrpl/ziag029","url":null,"abstract":"<p><p>Osteogenesis imperfecta (OI) encompasses a genetically diverse spectrum of skeletal dysplasias, commonly linked to pathogenic variants in <i>COL1A1</i> and <i>COL1A2</i>. Emerging data identify terminal nucleotidyltransferase 5A (<i>TENT5A</i>)-a noncanonical cytoplasmic poly(A) polymerase essential for mRNA stability of extracellular matrix (ECM) proteins-as a novel OI gene. However, human phenotypes associated with TENT5A impairment and its molecular underpinnings remain poorly characterized. We performed detailed clinical, biochemical, and transcriptomic characterization of a Palestinian male with homozygous <i>TENT5A</i> variant (NM_001370434: c.972C>G, p. Ile324Met). Functional studies were conducted on patient-derived fibroblasts subjected to osteogenic induction, assessing matrix mineralization, mRNA expression, poly(A) tail dynamics (via Nanopore direct RNA sequencing), and stress response. RNA-seq and qPCR were used to profile osteogenic and epigenetic gene expression. Despite normal stature and preserved long bone architecture, the proband exhibited recurrent small bone fractures and persistently elevated alkaline phosphatase. Fibroblasts from the proband demonstrated reduced mineralization and significantly shortened poly(A) tails in <i>COL1A1</i> and <i>COL1A2</i> transcripts, corresponding to decreased expression. Transcriptomic analysis revealed downregulation of key ECM, osteogenic, and chromatin-regulatory genes, alongside increased ribosomal transcripts and translational machinery. Poly(A) tail shortening was selective, affecting ECM and regulatory genes but sparing housekeeping genes. Under metabolic stress, <i>TENT5A</i>-impaired fibroblasts showed markedly reduced viability, indicating broader cellular vulnerability. Despite these molecular disruptions, clinical severity remained mild, possibly modulated by early bisphosphonate therapy. This case defines a distinct form of OI arising from post-transcriptional dysregulation in matrix-producing cells. <i>TENT5A</i> alteration compromises ECM production by destabilizing collagen mRNAs, disrupting osteogenic and epigenetic programs, and impairing cellular resilience. Our findings identify a novel homozygous <i>TENT5A</i> variant and demonstrate its pathogenic effect on osteoblast function and matrix mineralization, supporting the inclusion of <i>TENT5A</i> in diagnostic panels for unexplained skeletal fragility.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 4","pages":"ziag029"},"PeriodicalIF":3.0,"publicationDate":"2026-02-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13019700/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147574002","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 material strength index: differences by race/ethnicity in Caribbean Hispanic, non-Hispanic White, and non-Hispanic Black older US adults.","authors":"Luis Ortiz Vasquez, Carmen Germosen, Isabella Rosillo, Sanchita Agarwal, Ragyie Rawal, Ivelisse Colon, Mildense Del Orbe, Mariana Bucovsky, Mishaela Rubin, Marcella Walker","doi":"10.1093/jbmrpl/ziag027","DOIUrl":"10.1093/jbmrpl/ziag027","url":null,"abstract":"<p><p>Racial differences in fracture risk are not fully explained by differences in areal BMD (aBMD) as measured by DXA. Other aspects of bone quality, such as bone material properties, are not captured by DXA, but may contribute to fracture risk. Few studies have investigated racial/ethnic differences in bone material properties, and none have included Hispanic Americans. We assessed differences in bone material strength index (BMSi) measured by impact micro indentation by race/ethnicity. Caribbean Hispanic (CH), non-Hispanic Black (NHB), and non-Hispanic White (NHW) participants from the Washington Heights Inwood Community Aging Project (<i>N</i> = 148), a population-based study of aging in New York City, were included. While there were racial differences in aBMD, BMSi did not differ by race/ethnicity (CH vs NHB vs NHW: 79.3 ± 6.3 vs 78.3 ± 15 vs 77.7 ± 5.2) before (<i>p</i> = .22) or after (<i>p</i> = .47) adjustment for age, sex, BMI, fracture status, diabetes, alcohol consumption, smoking, and osteoporosis treatment. There was no significant interaction between race and diabetes status in relation to BMSi. Stratifying by sex, results were similar. In summary, BMSi was similar among CH, NHB, and NHW participants, suggesting that differences in bone material strength, as captured by BMSi, do not account for established racial/ethnic differences in fracture risk in these groups.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 4","pages":"ziag027"},"PeriodicalIF":3.0,"publicationDate":"2026-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12971002/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147432804","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":"Open and reproducible research in musculoskeletal imaging: why it matters and how to implement it with the guidelines of the Open and Reproducible Musculoskeletal Imaging Research (ORMIR) community.","authors":"Serena Bonaretti, Mojtaba Barzegari, Melissa Bevers, Steven Boyd, Andrew J Burghardt, Donnie Cameron, Francesco Chiumento, Gianluigi Crimi, Gerald Degenhart, Pholpat Durongbhan, Michelle Alejandra Espinosa Hernandez, Giulia Fraterrigo, Ali Ghasem-Zadeh, Lorenzo Grassi, Jukka Hirvasniemi, Seyedmahdi Hosseinitabatabaei, Gianluca Iori, Joeri Kok, Michael Kuczynski, YoungJun Lee, Cecilia Liberati, Sarah Manske, Matt McCormick, Maria Monzon, Martino Pani, Simone Poncioni, Jilmen Quintiens, Sabine Räuber, Paul Ritsche, Alfonso Dario Santamaria, Francesco Santini, Fabio Sarto, Enrico Schileo, Vincent Stadelmann, Kathryn S Stok, Rachel Surowiec, Fulvia Taddei, Jared Vicory, Matthias Walle, Mariska Wesseling, Danielle Whittier, Bettina Willie, Andy Kin On Wong, Dženan Zukić","doi":"10.1093/jbmrpl/ziag025","DOIUrl":"10.1093/jbmrpl/ziag025","url":null,"abstract":"<p><p>The Open and Reproducible Musculoskeletal Imaging Research community is a scientific community dedicated to promoting openness and reproducibility in musculoskeletal imaging, image processing, and computational modeling. In this perspective paper, we outline the motivations for conducting transparent research and provide practical guidelines for implementing it. We start by defining open and reproducible research and describing the benefits and challenges of working transparently. Next, we redefine the outputs of a computational research study as-ideally-a combination of data, code, and a publication, recommend a folder and file structure that reflects these three study outcomes, and describe how to maintain and update such a structure during the study and at study publication. Finally, we emphasize that working in an open and reproducible manner is a learning process, and the best way to acquire the necessary competencies is simply to start.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 4","pages":"ziag025"},"PeriodicalIF":3.0,"publicationDate":"2026-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13007879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147512238","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":"Marked regression of calcinosis with canakinumab in hyperphosphatemic familial tumoral calcinosis.","authors":"Astrid Dauchez, Julia Herrou, Fadila Mihoubi-Bouvier, Pierre Quartier, Geneviève Baujat, Eugénie Koumakis, Karine Briot, Christian Roux","doi":"10.1093/jbmrpl/ziag026","DOIUrl":"10.1093/jbmrpl/ziag026","url":null,"abstract":"<p><p>Hyperphosphatemic familial tumoral calcinosis (HFTC) is a rare autosomal recessive disease caused by pathogenic variants in genes involved in phosphate homeostasis, and characterized by elevated serum phosphate levels and the development of ectopic calcifications. Management typically includes phosphate-lowering strategies and, when clinically necessary, surgical debulking of calcifications. Inflammatory flares occur variably and remain poorly understood. We report the case of a 27-yr-old woman with HFTC due to a homozygous <i>GALNT3</i> mutation, who experienced recurrent painful flares, elevated inflammatory markers, and progressive calcinosis. Based on the hypothesis that HFTC may behave like an autoinflammatory syndrome, the patient was treated with canakinumab, an anti-interleukin-1 antibody, with 7 yr of follow-up to date. The treatment led to rapid and sustained clinical and biological remission, significant regression of calcified lesions without surgical intervention, and demonstrated good safety.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 4","pages":"ziag026"},"PeriodicalIF":3.0,"publicationDate":"2026-02-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12965204/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147377501","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":"Osteocytes regulate osteoprotegerin expression via the p38-MAPK-CREB pathway in rheumatoid arthritis.","authors":"Keitaro Yasumoto, Toshifumi Fujiwara, Toshiaki Sugita, Shinkichi Arisumi, Shotaro Kawamura, Takeshi Utsunomiya, Daisuke Hara, Shinya Kawahara, Ryosuke Yamaguchi, Yukio Akasaki, Satoshi Hamai, Goro Motomura, Hisakata Yamada, Yasuharu Nakashima","doi":"10.1093/jbmrpl/ziag023","DOIUrl":"10.1093/jbmrpl/ziag023","url":null,"abstract":"<p><p>Rheumatoid arthritis (RA) is accompanied by systemic and local bone loss, yet the regulation of osteoclast-modulating factors within human osteocytes under inflammatory conditions remains incompletely understood. As an exploratory study, we analyzed surgically resected femoral heads from patients with RA and osteoarthritis (OA). Micro-CT of standardized cancellous regions showed no significant differences in trabecular microarchitectural parameters between groups. In contrast, immunoblot analysis of cortical bone from the femoral neck demonstrated higher osteoprotegerin (OPG) protein levels in RA than in OA. To investigate the underlying mechanism, we examined osteocytes under inflammatory stimulation using the mouse osteocyte-like cell line MLO-Y4 and osteocyte-enriched bone fractions (OEBFs). Among tested cytokines, TNF-α most strongly induced osteoclast-regulatory transcripts and increased OPG protein levels and secretion. TNF-α activated p38-MAPK and cyclic adenosine monophosphate (AMP) response element-binding protein (CREB) signaling, and pharmacologic inhibition of either p38-MAPK activity or CREB activity reduced TNF-α-induced OPG protein accumulation. Chromatin immunoprecipitation (ChIP) further showed enhanced recruitment of CREB to a responsive region within the OPG promoter after TNF-α stimulation. Finally, osteocyte-conditioned medium altered osteoclast morphology and reduced expression of an osteoclast lineage marker during RANKL-driven differentiation, while OPG neutralization did not produce a dominant reversal of these effects. Together, these findings indicate that OPG is upregulated in femoral neck cortical bone from patients with RA and that TNF-α can enhance osteocytic OPG expression via a p38-MAPK-CREB axis, alongside additional osteocyte-derived factors that modulate osteoclast maturation. This study provides evidence from human femoral head specimens of increased OPG in RA cortical bone and suggests that the p38-MAPK-CREB axis may represent an underappreciated regulatory component of osteocyte-derived OPG under inflammatory conditions.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 4","pages":"ziag023"},"PeriodicalIF":3.0,"publicationDate":"2026-02-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12971003/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147432809","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":"IGF-1 from bone marrow Adipoq-lineage cells stimulates endocortical bone formation in mature female mice.","authors":"Joshua C Bertels, Jasmin Koehnken Sawall, Brian Dulmovits, Xiaobin Liu, Ashley Phan, Xing Ji, Fangfang Song, Christopher Thom, Fanxin Long","doi":"10.1093/jbmrpl/ziag024","DOIUrl":"10.1093/jbmrpl/ziag024","url":null,"abstract":"<p><p>Insulin-like growth factor 1 (IGF-1) is an anabolic signal promoting growth, differentiation and function of both embryonic and postnatal tissues. Both endocrine and paracrine functions of IGF-1 have been documented to regulate bone growth and BM hematopoiesis. Local production of IGF-1 from various cell types may contribute differently to the overall bioactivity of IGF-1 in bone, but relevant sources and mechanisms are yet to be fully elucidated. Here, we report that the Adipoq⁺ stromal cells are a notable source of IGF-1 in the BM of postnatal mice. Deletion of IGF-1 with Adipoq-Cre diminished endocortical bone formation and cortical bone mass in mature female mice. On the other hand, the trabecular bone parameters or hematopoietic properties were not affected in mutant mice of either sex. The study uncovers a local source of IGF-1 in the BM microenvironment that contributes to bone anabolic regulation in a site-specific manner.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 4","pages":"ziag024"},"PeriodicalIF":3.0,"publicationDate":"2026-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12965202/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147377493","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":"Upper arm administration is associated with higher injection site pain with romosozumab: a randomized controlled trial and a self-controlled study.","authors":"Soji Tani, Tomoyuki Asada, Hiro Hasegawa, Peter Passias, Koki Tsuchiya, Mahoko Ishikawa, William Richardson, Yoshifumi Kudo, Benjamin Alman, Koji Ishikawa","doi":"10.1093/jbmrpl/ziag022","DOIUrl":"10.1093/jbmrpl/ziag022","url":null,"abstract":"<p><p>These 2 prospective studies investigated whether the injection site influences pain and local reactions with romosozumab treatment for osteoporosis. In Study 1, 169 patients were randomly assigned to receive monthly romosozumab 210 mg (2 vials) injections for 12 mo in either the abdomen (Abd group) or upper arm (Arm group). In Study 2, 55 patients received 105 mg (1 vial) injections in both sites to directly compare pain at each location. Pain was evaluated using a Visual Analog Scale (VAS, mm), and secondary outcomes included BMD, bone turnover markers (BTMs) (total P1NP and TRACP-5b), and injection site reactions (ISRs). In the randomized trial, 70 of 85 patients (82.4%) in the Abd group and 69 of 84 (82.1%) in the Arm group completed the study. The Arm group reported significantly greater pain than the Abd group, starting after the fifth injection (mean difference, 6.8 mm [95% CI, 0.7-12.8]; <i>p</i> = .029) and continuing through the 12th injection (9.5 mm [95% CI, 2.9-16.1]; <i>p</i> = .005). Although crude ISR rates were similar (Abd, 26.2% vs Arm, 35.8%; <i>p</i> = .24), multivariable analysis showed a higher ISR incidence in the Arm group (incidence rate ratio: 1.73 [95% CI, 1.01-2.95]; <i>p</i> = .045). In Study 2, pain was consistently greater at the upper arm, beginning with the first injection (mean difference, 5.2 mm [95% CI, 1.7-8.7]; <i>p</i> = .004) and continuing through the 12th (8.1 mm [95% CI, 4.2-11.9]; <i>p</i> < .001). BMD and BTMs did not differ between sites. In conclusion, upper arm injections were associated with greater pain and higher ISR incidence without affecting bone metabolism. Selecting an injection site based on comfort may improve patient experience during romosozumab therapy.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 4","pages":"ziag022"},"PeriodicalIF":3.0,"publicationDate":"2026-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12965206/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147377559","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":"β₂-adrenoceptor signaling in chondrocytes regulates long bone growth, bone homeostasis, and fracture healing in mice.","authors":"Melanie Rebecca Kuhn, Melanie Haffner-Luntzer, Sandra Dieterich, Meike Sachs, Gundula Rösch, Zsuzsa Jenei-Lanzl, Stefan Oskar Reber, Anita Ignatius, Miriam Eva Angelica Tschaffon-Müller","doi":"10.1093/jbmrpl/ziag021","DOIUrl":"10.1093/jbmrpl/ziag021","url":null,"abstract":"<p><p>Catecholamines are known to interact with bone and cartilage cells via binding to adrenergic receptors. Among these, the β₂-adrenoceptor (β₂-AR) plays a key role in mediating the effects of catecholamines on bone. Mice lacking the β₂-AR systemically or specifically in osteoblasts show an increased bone mass. Previous studies further indicated an important influence of catecholamines on transdifferentiation of chondrocytes towards osteoblasts during endochondral ossification. Therefore, in this study, cartilage and bone phenotype as well as fracture healing of mice with a specific knockout of the β₂-AR in chondrocytes were investigated. Tibiae and femora of 6-, 12-, and 40-wk-old male and female mice were analyzed. The knockout resulted in a reduced long bone growth, most likely due to a faster transition of proliferative to hypertrophic chondrocytes. The older knockout mice additionally showed an osteopenic bone phenotype due to a reduced number of osteoblasts. Fracture healing after a standardized femur osteotomy was delayed, showing reduced cartilage area at an intermediate time point during fracture healing. Gene expression analysis in an additional in-vitro-experiment identified pathways like \"Wnt-signaling\" and \"TGFβ-signaling\" to be involved. In conclusion, our data showed an important role of the β₂-AR specifically in chondrocytes during long bone growth, bone homeostasis in older animals and fracture healing.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 4","pages":"ziag021"},"PeriodicalIF":3.0,"publicationDate":"2026-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12971017/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147432757","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":"Association between chronic inflammation and poorer long-term functional recovery post-hip fracture in and between men and women.","authors":"Marty Eastlack, Zhaoyong Feng, Laurence S Magder, Ram R Miller, Denise L Orwig, Ann Gruber-Baldini, Jay Magaziner, Alice S Ryan","doi":"10.1093/jbmrpl/ziag019","DOIUrl":"10.1093/jbmrpl/ziag019","url":null,"abstract":"<p><p>Mechanisms underlying functional recovery after hip fracture have not been widely studied in either sex, but particularly not in men. Cytokines, or biomarkers of inflammation in the blood, are associated with declines in function post hip fracture in women. Therefore, the aim of this study was to examine chronic systemic inflammation, as measured by cytokines, and its association with function and functional recovery post-hospitalization within and between the sexes. In the sample, with equal proportions of men and women, cytokines were measured at baseline, 2, 6, and 12 mo post-hip fracture, including IL1-ra, IL-6, and sTNFα-R1 levels. The Short Physical Performance Battery (SPPB) was measured at 2 and 6 mo. Participants were divided into tertiles based on their 2-mo cytokine levels. Longitudinal regression models were used to examine the change in cytokine levels over the year by sex, and to model the association of cytokine tertiles and physical function. Older adults (<i>n</i> = 311, 50% men, age 80.9 ± 7.5 yr) were included. Men had higher levels of IL-6 and sTNFα-R1 at 2, 6, and 12 mo. Lower 2-mo cytokine levels were associated with better function at 2 mo and better recovery of function at 6-mo. Women in the lowest tertile of IL-6 and sTNFα-R1 at 2 mo had higher SPPB scores (all <i>p</i> ≤ .03) than men in the middle and upper tertiles, and these findings persisted at 6 mo. Furthermore, women in the lowest tertile of IL1-ra had better recovery in the SPPB than men in all tertiles at 6 mo (<i>p</i> ≤ .03). Lower levels of systemic inflammation were associated with better functional performance at 2 mo and functional recovery at 6 mo post hip fracture. The between sex differences in cytokines and functional recovery suggest that medical management and rehabilitation strategies may need to be adapted by sex and with attention to specific inflammatory biomarkers.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":"10 4","pages":"ziag019"},"PeriodicalIF":3.0,"publicationDate":"2026-02-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC13019678/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"147573985","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}