Bone最新文献

{"title":"Investigating the role of complement 5a in systemic bone loss after myocardial infarction","authors":"Priscilla M. Tjandra ,&nbsp;Sophie V. Orr ,&nbsp;Selena K. Lam ,&nbsp;Anika D. Kulkarni ,&nbsp;Yi-Je Chen ,&nbsp;Anna Adhikari ,&nbsp;Jill L. Silverman ,&nbsp;Crystal M. Ripplinger ,&nbsp;Blaine A. Christiansen","doi":"10.1016/j.bone.2025.117543","DOIUrl":"10.1016/j.bone.2025.117543","url":null,"abstract":"<div><div>Myocardial infarction (MI) and osteoporotic fracture are two of the leading causes of morbidity and mortality worldwide. We have previously established that MI in mice directly causes post-traumatic systemic bone loss and that the sympathetic nervous system plays a role in this response. However, the systemic injury response is mediated by multiple systems. In this study, we investigated the role of complement 5a (C5a), one of the main mediators driving multiple organ dysfunction after trauma. MI was surgically induced in 12-week-old male C57BL/6 J mice (B6/J), C5a receptor 1 knockout mice (<em>C5aR1</em>^{<em>−/−</em>}) and B10·D2-Hc0 H2d H2-T18c/oSnJ (B10·D2), (JAX Strain # 000461) mice that are deficient in serum C5. Systemic and localized bone changes were analyzed at 7-, 14- and 28-days post-MI using micro-computed tomography and three-point bending mechanical testing. Osteoclast number and activity was quantified using tartrate-resistant acid phosphatase (TRAP) staining, and voluntary activity levels were measured using open field. We found that MI induced peak trabecular bone loss 7 days after injury in the L5 vertebral body and caused reductions in femoral cortical bone 28 days post-MI. However, MI did not impact femoral trabecular bone in this timeframe. B10·D2 mice had reduced trabecular and cortical bone morphology compared to B6 and <em>C5aR1</em>^−/− mice, but did not exhibit an altered response to MI. Osteoclast activity 7-days post-MI was increased in <em>C5aR1</em>^−/− mice compared to B6 and B10·D2 mice, but MI did not impact osteoclast activity at this time point. Altogether, these findings suggest that C5a may influence overall response to MI and bone morphology instead of post-traumatic systemic bone loss response following MI, though likely not as a primary mechanism.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"198 ","pages":"Article 117543"},"PeriodicalIF":3.5,"publicationDate":"2025-05-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144144798","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":"Markedly discordant hypophosphatasia in a young girl","authors":"Vikram Prakash ,&nbsp;Samer Elbabaa ,&nbsp;Richard Banks ,&nbsp;Gabriel de Carlos ,&nbsp;William H. McAlister ,&nbsp;Steven Mumm ,&nbsp;Michael P. Whyte","doi":"10.1016/j.bone.2025.117541","DOIUrl":"10.1016/j.bone.2025.117541","url":null,"abstract":"<div><div><em>Hypophosphatasia</em> (HPP) is the inborn-error-of-metabolism from deactivating mutation(s) of <em>ALPL</em>, the gene that encodes the cell surface “tissue-nonspecific” isoenzyme of alkaline phosphatase (TNSALP). HPP's “biochemical signature” comprises low serum alkaline phosphatase activity together with elevated plasma levels of the TNSALP natural substrates phosphoethanolamine (PEA), pyridoxal 5′-phosphate (PLP), and inorganic pyrophosphate (PPi). Excess extracellular PPi (ePPi) inhibits mineralization and affected children prematurely shed deciduous teeth and often suffer weakness and rickets. Yet, HPP severity is greatest among all dento-osseous disorders and not fully explained by autosomal dominant versus autosomal recessive inheritance involving &gt;470 <em>ALPL</em> mutations. Discordance of HPP phenotype sometimes manifests even among full siblings sharing an identical <em>ALPL</em> genotype.</div><div>Herein, a girl's markedly discordant HPP featured at presentation life-threatening hypercalcemia, failure-to-thrive, and renal compromise. Subsequent pseudotumor cerebri syndrome caused blindness, and then craniosynostosis required cranial vault reconstruction. However, she was not deformed, had moderate hypophosphatasemia, normal plasma PLP level, and mild radiographic features of HPP rickets. Elevated plasma N-terminal parathyroid hormone-related protein (PTHrP) suggested malignancy, but corrected after kidney transplantation. HPP was diagnosed when whole exome sequencing revealed heterozygous <em>ALPL</em> c.1034C&gt;T, p.A345V found in mild pediatric HPP and transmitted by her mother who considered herself well. Genes conditioning ePPi formation and underlying other skeletal diseases were intact. Hypercalcemia, unresponsive to bone antiresorptive drugs, corrected promptly with asfotase alfa TNSALP supplementation therapy. Her markedly discordant findings highlight genotype/phenotype plasticity for pediatric HPP, and her clinical course importance for early diagnosis.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"199 ","pages":"Article 117541"},"PeriodicalIF":3.5,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133148","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":"A partnership between the Australian and New Zealand Bone and Mineral Society (ANZBMS) and Bone: Highlights from the 2024 annual scientific meeting","authors":"Marc Sim ,&nbsp;Kylie A. Alexander ,&nbsp;Natalie A. Sims ,&nbsp;Ian R. Reid ,&nbsp;Mark Forwood","doi":"10.1016/j.bone.2025.117540","DOIUrl":"10.1016/j.bone.2025.117540","url":null,"abstract":"<div><div>The Australian and New Zealand Bone and Mineral Society (ANZBMS) is a leading bone research society in the Asia-Pacific region and has been recognised for outstanding contributions to clinical and biomedical musculoskeletal research. To showcase the research being undertaken by ANZBMS members, a joint initiative between ANZBMS and the journal Bone via a special issue was developed to further enhance international collaboration. This editorial serves as an introduction to this initiative, where three past ANZBMS presidents have shared their clinical and fundamental highlights from the 2024 ANZBMS annual scientific meeting in Adelaide, held in conjunction with the Endocrine Society of Australia and the Society for Reproductive Biology. Highlights include the importance of ethnicity when considering fracture risk, influence of paternal age on bone health in their offspring, novel combinations of bone active medications, bone biology and cancer, effect of glucocorticoids on the formation of neurogenic heterotopic ossification, parathyroid hormone signalling in hematopoietic and osteogenic lineages in the bone microenvironment and the regulation of osteoclast formation. Through a highly regarded platform such as Bone, and in line with the wider aims of the ANZBMS, this collaboration provides an update on the work being conducted by members of the society.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"198 ","pages":"Article 117540"},"PeriodicalIF":3.5,"publicationDate":"2025-05-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144133118","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 role of the extracellular matrix protein SPOCK2 for bone physiology and hematopoiesis","authors":"Rahul Kumar ,&nbsp;Subhadeep Das ,&nbsp;Wahyu Minka ,&nbsp;Celina Reiter ,&nbsp;Raquel Pereira ,&nbsp;Dominik Fuhrmann ,&nbsp;Richard Schneider ,&nbsp;Anita Seshire ,&nbsp;Christof Reusch ,&nbsp;Claire Conche ,&nbsp;Katharina Imkeller ,&nbsp;Paola Divieti Pajevic ,&nbsp;Daniela S. Krause","doi":"10.1016/j.bone.2025.117539","DOIUrl":"10.1016/j.bone.2025.117539","url":null,"abstract":"<div><div>The bone marrow microenvironment (BMM) consists of different cellular and acellular components. These components synergize in regulating the process of hematopoiesis. Various extracellular matrix proteins are found amongst the acellular components. Secreted protein acidic and rich in cysteine (SPARC) is amongst the most abundant glycoproteins in bone. Sparc/osteonectin, cwcv, and Kazal-like domains proteoglycan 2 (SPOCK2) is a member of the SPARC family, and its role in bone metabolism and hematopoiesis has not been investigated. Using female mice deficient for SPOCK2, we assessed the role of SPOCK2 in influencing bone formation, the BMM and hematopoiesis. Using micro-computed tomography we found a significant decrease in trabecular bone volume, bone mineral density and thickness, but increased cortical mineral density in SPOCK2 knockout (KO) versus wildtype (WT) bones. C-terminal telopeptide of type I collagen, a measure of bone resorption, was significantly increased in bone marrow supernatants of SPOCK2 KO mice. In the hematopoietic compartment we found an increase in hematopoietic stem cells, but a decrease of mesenchymal stromal cells and adipocytes in the bone marrow of SPOCK2 KO mice compared to control mice. Megakaryocytes were increased in SPOCK2 KO mice. In summary, deficiency of SPOCK2 leads to several alterations in the BMM. The hematopoietic effects may be due to hematopoietic cell-intrinsic effects in SPOCK2-deficient cells or due to a SPOCK2-deficient niche or both.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"198 ","pages":"Article 117539"},"PeriodicalIF":3.5,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144116795","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":"Linagliptin-metformin combination: A novel approach to mitigate 4-vinyl cyclohexene di epoxide and dexamethasone-induced osteoporosis in mice","authors":"Nikita Nirwan,&nbsp;Shreshta Jain,&nbsp;Divya Vohora","doi":"10.1016/j.bone.2025.117526","DOIUrl":"10.1016/j.bone.2025.117526","url":null,"abstract":"<div><div>Elevated levels of dipeptidyl-peptidase (DPP-4) enzyme, associated with accelerated bone resorption, are linked to both post-menopausal osteoporosis (PMO) and glucocorticoid-induced osteoporosis (GIO). Consequently, DPP-4 inhibitors, a class of anti-diabetic drugs, emerge as potential candidates for repurposing as anti-osteoporotic agents. In this study, we explored the effect of 4-week treatment with linagliptin (a DPP-4 inhibitor) and its combination with metformin on PMO and GIO in mice. PMO was induced in Balb/c mice by injecting 4-vinyl cyclohexene diepoxide (VCD), 160 mg/kg, ip for 15 days while GIO was induced by administering dexamethasone (DEX) 5 mg/kg, ip for 21 days. A significant improvement in bone architectural parameters and bone mineral density (BMD) was observed following the linagliptin-metformin combination, which was consistent with the altered bone turnover markers <em>i.e.</em>, increased ALP, osteocalcin, BMP-2, and reduced serum calcium, TRAP, sclerostin and pro-inflammatory cytokines. Results from bone immunohistochemistry (IHC) demonstrated that the combination led to an increase in immunopositive OPG cells, while RANKL expression was diminished. Linagliptin, however, demonstrated only partial improvement in the PMO model. Conversely, in the GIO model, linagliptin did not show a significant effect except for improved BMD and sclerostin levels. Treatment with metformin did not show significant changes in either model. These findings suggest that the combination of linagliptin with metformin could alleviate the PMO and GIO, possibly through targeting AMPK and Wnt signaling pathway and thereby modulating BMP-2, sclerostin and RANKL/OPG.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"198 ","pages":"Article 117526"},"PeriodicalIF":3.5,"publicationDate":"2025-05-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144121648","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":"Col1a2oim/oim mice exhibit alterations in ossicular bone quality typical of osteogenesis imperfecta but no hearing loss","authors":"Ana Ocokoljic ,&nbsp;Maximilian M. Delsmann ,&nbsp;Simon von Kroge ,&nbsp;Timur A. Yorgan ,&nbsp;Tobias M. Ballhause ,&nbsp;Assil-Ramin Alimy ,&nbsp;Felix N. von Brackel ,&nbsp;Frank Timo Beil ,&nbsp;Lukas Rüttiger ,&nbsp;Ralf Oheim ,&nbsp;Mark Praetorius ,&nbsp;Tim Rolvien","doi":"10.1016/j.bone.2025.117537","DOIUrl":"10.1016/j.bone.2025.117537","url":null,"abstract":"<div><div>Osteogenesis imperfecta (OI) is an inherited connective tissue disorder clinically mainly characterized by skeletal fragility. However, non-skeletal manifestations, some of which do not appear until adulthood, can additionally severely impact the health and quality of life of the affected patients. These include hearing loss that is observed in approximately every second OI patient. While the hearing loss in OI is mainly due to impaired sound transmission (i.e., conductive hearing loss), the underlying mechanisms are currently elusive. Here, we investigated the <em>Oim</em> (<em>Col1a2</em>^{<em>oim/oim</em>}) mouse model of classical OI, focusing on bone quality features of the middle ear and hearing function. No osseous morphological changes were observed in the middle or inner ear of male <em>Col1a2</em>^{<em>oim/oim</em>} mice compared to wildtype controls. Backscattered electron imaging and Fourier-transform infrared spectroscopy revealed increased matrix mineralization and matrix maturity of the auditory ossicles (malleus, stapes). These changes have previously been described as typical features of OI in other skeletal regions. However, measurement of auditory function by auditory brainstem response revealed no gross hearing pathology and even indicated a slightly improved hearing ability in <em>Col1a2</em>^{<em>oim/oim</em>} mice in the 32 kHz range as determined by distortion product otoacoustic emissions (DPOAEs). Taken together, our results indicate that the conductive hearing loss observed in classical OI is not due to the altered bone quality of the middle ear, at least under unchallenged conditions in mice.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"198 ","pages":"Article 117537"},"PeriodicalIF":3.5,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144106609","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":"Dentoalveolar defects and impaired alveolar bone healing in a neural crest directed conditional knockout mouse model of hypophosphatasia","authors":"F.F. Mohamed ,&nbsp;A. Phanrungsuwan ,&nbsp;F. Amadeu de Oliveira ,&nbsp;J.L. Millán ,&nbsp;B.L. Foster","doi":"10.1016/j.bone.2025.117538","DOIUrl":"10.1016/j.bone.2025.117538","url":null,"abstract":"<div><div>Hypophosphatasia (HPP) is an inherited error-of-metabolism caused by loss-of-function mutations in <em>ALPL</em>-encoded tissue-nonspecific alkaline phosphatase (TNAP). HPP has wide-ranging severity, including a clinical subtype called odontohypophosphatasia (odonto HPP), which selectively affects craniofacial structures. Dentoalveolar defects in HPP can affect enamel, dentin, and alveolar bone, and deficient acellular cementum contributes to tooth loss. Global <em>Alpl</em> knockout phenocopies effects of severe HPP, but early lethality precludes longer-term studies. Aiming to create a mouse model replicating dentoalveolar effects of HPP, we used <em>Wnt1</em>^{<em>Cre2</em>} mice to conditionally delete <em>Alpl</em> in ectomesenchymal cells that make dentin, cementum, periodontal ligament (PDL), and alveolar bone. We compared appendicular and craniofacial skeletal effects of <em>Wnt1</em>^{<em>Cre2</em>} to <em>Prx1</em>^<em>Cre</em> conditional <em>Alpl</em> ablation in limb bud mesenchyme. We also tested alveolar bone socket healing in <em>Wnt1</em>^{<em>Cre2</em>}; <em>Alpl</em>^{<em>fl/fl</em>} conditional knockout mice and the effect of TNAP-Fc-D₁₀ enzyme replacement therapy (ERT) on socket healing. <em>Prx1</em>^<em>Cre</em>; <em>Alpl</em>^{<em>fl/fl</em>} mice exhibited 38 % reduced circulating alkaline phosphatase (ALP) and long bone defects, but no craniofacial phenotypes. <em>Wnt1</em>^{<em>Cre2</em>}; <em>Alpl</em>^{<em>fl/fl</em>} mice featured 60 % reduced ALP and profound mineralization defects in dentin, cementum, and alveolar bone, but no appendicular skeleton changes. Defects were noted in neural crest-derived intersphenoid synchondrosis of the cranial base and mandibular condyle of <em>Wnt1</em>^{<em>Cre2</em>}; <em>Alpl</em>^{<em>fl/fl</em>} mice. Extraction of maxillary molars in <em>Wnt1</em>^{<em>Cre2</em>}; <em>Alpl</em>^{<em>fl/fl</em>} mice revealed profound alveolar bone healing defects that were partially rescued by ERT. Cranial neural crest deletion of <em>Alpl</em> resulted in a mouse model phenocopying odonto HPP that can be used to investigate mechanisms underlying pathologies as well as interventions.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"198 ","pages":"Article 117538"},"PeriodicalIF":3.5,"publicationDate":"2025-05-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144089970","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":"Intracellular Staphylococcus aureus in osteoblasts and osteocytes and its impact on bone homeostasis during osteomyelitis","authors":"Quentin Collet ,&nbsp;Frédéric Velard ,&nbsp;Frédéric Laurent ,&nbsp;Jérôme Josse","doi":"10.1016/j.bone.2025.117536","DOIUrl":"10.1016/j.bone.2025.117536","url":null,"abstract":"<div><div>Osteomyelitis is a severe infection of bone tissue that can lead to bone loss and even osteonecrosis. This condition is mostly caused by Gram-positive bacteria, with <em>Staphylococcus aureus</em> being the most common etiological agent. Among the pathophysiological mechanisms involved in osteomyelitis, the ability of <em>S. aureus</em> to be internalized by osteoblasts or osteocytes and to survive within these cells, is particularly noteworthy. Infected osteoblasts and osteocytes not only serve as reservoirs in chronic cases of osteomyelitis but also play an active role in the osteoimmunology process, notably by producing mediators that promote the bone resorption activity of osteoclasts, thereby disrupting bone homeostasis. The present review explores both historical and recent literature on the internalization of <em>S. aureus</em> by osteoblasts and osteocytes, its intracellular behavior following internalization, and its mechanisms for inducing cell death. Additionally, it examines how <em>S. aureus</em> affects bone formation activity and promotes the production of inflammatory and pro-osteoclastic mediators. This review aims to highlight the limitations of current findings and outline key questions for future investigations.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"198 ","pages":"Article 117536"},"PeriodicalIF":3.5,"publicationDate":"2025-05-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144089967","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 mineral density deficits in individuals born preterm persist through young adulthood: A systematic review and meta-analysis of DXA studies","authors":"Brittany M. Wilson ,&nbsp;Adam B. Wilson ,&nbsp;Megan Kraemer ,&nbsp;Rakhee Bowker ,&nbsp;Aloka L. Patel ,&nbsp;D. Rick Sumner","doi":"10.1016/j.bone.2025.117519","DOIUrl":"10.1016/j.bone.2025.117519","url":null,"abstract":"<div><div>Individuals born preterm are at increased risk for bone deficits given that the majority of skeletal mineral accrual occurs during the final gestational trimester. It is unclear how preterm birth affects bone density with aging or if individuals born preterm have increased rates of osteoporosis. This systematic review and meta-analysis summarizes the current data on bone mineral content and density measured by dual-energy x-ray absorptiometry (DXA) at any time across the lifespan after preterm birth in generally healthy, appropriate size for gestational age individuals. Three databases, including PubMed, Scopus, and CINAHL, were searched using keywords related to preterm birth and skeletal mineralization. Total body, lumbar spine, and femoral neck were the most frequently reported DXA measurement sites. A total of 39 studies (145 comparisons) were included in the meta-analyses, with bone outcomes measured within days of birth through about 30 years of age, depending on the measurement site. Preterm birth was associated with reduced bone mineral content and density. The largest total body bone deficits were observed in preterm individuals who were less than one year of age, with greater variability observed during childhood and adolescence. Individuals born preterm in the oldest cohort (17–30 years) maintained deficits in bone mineral density as they approached the age of peak bone mass. Importantly, there were no DXA studies of preterm individuals beyond 30 years of age, so it remains unclear how preterm birth affects the skeleton with advanced aging.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"198 ","pages":"Article 117519"},"PeriodicalIF":3.5,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103286","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":"Skeletal response to Yoda1 and whole-body vibration in mice varied with animal age, bone compartment, treatment duration, and radiation exposure","authors":"Tiankuo Chu ,&nbsp;Murtaza Wasi ,&nbsp;Rosa M. Guerra ,&nbsp;Xin Song ,&nbsp;Shubo Wang ,&nbsp;Jennifer Sims-Mourtada ,&nbsp;Lidan You ,&nbsp;Liyun Wang","doi":"10.1016/j.bone.2025.117525","DOIUrl":"10.1016/j.bone.2025.117525","url":null,"abstract":"<div><div>In this study, we investigated the skeletal effects of Yoda1, an agonist of the mechanosensitive Piezo1 channels, and whole-body vibration (WBV), alone and combined, in young mice (8-week-old) and in mature (31- to 36-week-old) mice after radiation exposure. Our goal was to determine whether the two mechanobiology-based interventions, known to induce anabolic response individually in young subjects, could promote bone health of older subjects undergoing cancer treatments such as radiotherapy. Our hypothesis was that the combination of Yoda1 and WBV could improve young skeletons and protect mature skeletons after radiotherapy better than Yoda1 or WBV alone. Our in vivo experiments demonstrated (1) that Yoda1 (5 mg/kg body weight) alone or combined with WBV (0.3 g, 13 Hz, 30 min/day, 5 days/week, 4 weeks) enhanced bone growth similarly (∼2 folds relative to nontreated controls) in young mice; (2) that mature mice were unresponsive to individual interventions but exhibited less polar moment of inertia loss (−56 %) in the tibiae receiving the combination of Yoda1 and WBV (15 min/day) but no radiation exposure; and (3) that the contralateral tibiae receiving fractionated radiation (2 × 8 Gy over three days) did not show different treatment responses in Week 4, while they responded to the combination therapy (increased cortical bone formation) in Week 2. Interestingly, pair comparisons of the irradiated and non-irradiated tibiae of the same animals revealed that radiation exposure resulted in decreased trabecular bone loss regardless of the treatments and increased the percentage of tibiae maintaining better cortical polar moment of inertia and cortical area in the groups receiving Yoda1 or the combination therapy. The complex skeletal responses to Yoda1 and/or WBV were compartment specific (cortical or trabecular bone) and dependent on animal age, radiation exposure, and treatment duration. This study partially supported our original hypothesis, while suggesting the need of finetuning the Yoda1 and WBV regimens and elucidating the underlying mechanisms in order to effectively treat age and radiation induced bone loss.</div></div>","PeriodicalId":9301,"journal":{"name":"Bone","volume":"198 ","pages":"Article 117525"},"PeriodicalIF":3.5,"publicationDate":"2025-05-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144103288","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}