JBMR Plus最新文献

{"title":"Mouse mandibular-derived osteoclast progenitors have differences in intrinsic properties compared with femoral-derived progenitors.","authors":"Rachel Clark, Soo Y Park, Elizabeth W Bradley, Kim Mansky, Amy Tasca","doi":"10.1093/jbmrpl/ziae029","DOIUrl":"10.1093/jbmrpl/ziae029","url":null,"abstract":"<p><p>Craniofacial osteoclasts are essential for site-specific processes such as alveolar bone resorption, tooth eruption, and orthodontic tooth movement. Much of the current understanding of osteoclast development and function comes from studies using long bone-derived cells. Minimal investigation has been done to explore skeletal site differences. The overall goal of this study was to determine if mandibular- and femoral-derived osteoclasts represent distinct populations. To test this hypothesis, bone marrow cells were initially analyzed from the mandible and femur of 2-month-old mice. It was shown that mandibular-derived osteoclasts have enhanced size (mm²) compared with femoral-derived osteoclasts. Since bone marrow macrophages are a heterogenous population, we additionally selected for monocytes and demonstrated that mandibular-derived monocytes also form osteoclasts with increased size compared with femoral-derived monocytes. Osteoclast precursor populations from both skeletal sites were analyzed by flow cytometry. A newly described Ly6C^High+ population as well as the Ly6C^int population was increased in the mandibular-derived cells. The difference in differentiation potential between monocyte cultures suggests that the increase in the Ly6C^High+ population may explain the enhanced differentiation potential in mandibular-derived cells. Monocyte genes such as <i>Pu.1</i>, <i>C/ebp-a,</i> and <i>Prdm1</i> are increased in expression in mandibular-derived monocytes compared with femoral-derived monocytes. As expected with enhanced differentiation, osteoclast genes including <i>Nfatc1, Dc-stamp, Ctsk</i>, and <i>Rank</i> are upregulated in mandibular-derived osteoclast precursors. Future studies will determine how changes in the environment of the mandible lead to changes in percentages of osteoclast progenitors and their differentiation potential.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.4,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11008737/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140869915","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":"A homozygous <i>SP7/OSX</i> mutation causes osteogenesis and dentinogenesis imperfecta with craniofacial anomalies.","authors":"Dalal A Al-Mutairi, Ali A Jarragh, Basel H Alsabah, Marc N Wein, Wasif Mohammed, Lateefa Alkharafi","doi":"10.1093/jbmrpl/ziae026","DOIUrl":"10.1093/jbmrpl/ziae026","url":null,"abstract":"<p><p>Osteogenesis imperfecta (OI) is a heterogeneous spectrum of hereditary genetic disorders that cause bone fragility, through various quantitative and qualitative defects of type 1 collagen, a triple helix composed of two α1 and one α2 chains encoded by <i>COL1A1</i> and <i>COL1A2</i>, respectively. The main extra-skeletal manifestations of OI include blue sclerae, opalescent teeth, and hearing impairment. Moreover, multiple genes involved in osteoblast maturation and type 1 collagen biosynthesis are now known to cause recessive forms of OI. In this study a multiplex consanguineous family of two affected males with OI was recruited for genetic screening. To determine the causative, pathogenic variant(s), genomic DNA from two affected family members were analyzed using whole exome sequencing, autozygosity mapping, and then validated with Sanger sequencing. The analysis led to the mapping of a homozygous variant previously reported in SP7/OSX, a gene encoding for Osterix, a transcription factor that activates a repertoire of genes involved in osteoblast and osteocyte differentiation and function. The identified variant (c.946C > T; p.Arg316Cys) in exon 2 of <i>SP7/OSX</i> results in a pathogenic amino acid change in two affected male siblings and develops OI, dentinogenesis imperfecta, and craniofacial anomaly. On the basis of the findings of the present study, <i>SP7/OSX</i>:c. 946C > T is a rare homozygous variant causing OI with extra-skeletal features in inbred Arab populations.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-03-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10984723/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335592","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: Interspecies Single Cell RNA Seq Analysis Reveals the Novel Trajectory of Osteoclast Differentiation and Therapeutic Targets","authors":"","doi":"10.1093/jbmrpl/ziae030","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae030","url":null,"abstract":"","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-03-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140271679","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Chromatin accessibility profiling reveals that human fibroblasts respond to mechanical stimulation in a cell-specific manner.","authors":"Niall J Logan, Krystyna L Broda, Nikolaos Pantelireis, Greg Williams, Claire A Higgins","doi":"10.1093/jbmrpl/ziae025","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae025","url":null,"abstract":"<p><p>Fibroblasts in the skin are highly heterogeneous, both in vivo and in vitro. One difference between follicular (dermal papilla fibroblasts [DP]) and interfollicular fibroblasts (papillary fibroblasts [PFi]) in vitro is their ability to differentiate in response to osteogenic media (OM), or mechanical stimulation. Here, we asked whether differences in the ability of DP and PFi to respond to differentiation stimuli are due to differences in chromatin accessibility. We performed chromatin accessibility and transcriptional profiling of DP and PFi in human skin, which arise from a common progenitor during development, yet display distinct characteristics in adult tissue and in vitro. We found that cells cultured in growth media had unique chromatin accessibility profiles; however, these profiles control similar functional networks. Upon introduction of a chemical perturbation (OM) to promote differentiation, we observed a divergence not only in the accessible chromatin signatures but also in the functional networks controlled by these signatures. The biggest divergence between DP and PFi was observed when we applied 2 perturbations to cells: growth in OM and mechanical stimulation (a shock wave [OMSW]). DP readily differentiate into bone in OMSW conditions, while PFi lack differentiation capability in vitro. In the DP we found a number of uniquely accessible promoters that controlled osteogenic interaction networks associated with bone and differentiation functions. Using ATAC-seq and RNA-seq we found that the combination of 2 stimuli (OMSW) could result in significant changes in chromatin accessibility associated with osteogenic differentiation, but only within the DP (capable of osteogenic differentiation). De novo motif analysis identified enrichment of motifs bound by the TEA domain (TEAD) family of transcription factors, and inter-cell comparisons (UpSet analysis) displayed large groups of genes to be unique to single cell types and conditions. Our results suggest that these 2 stimuli (OMSW) elicit cell-specific responses by modifying chromatin accessibility of osteogenic-related gene promoters.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-02-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11055960/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140850272","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":"The impact of age and sex on the inflammatory response during bone fracture healing.","authors":"Kristin Happ Molitoris, Abhinav Reddy Balu, Mingjian Huang, Gurpreet Singh Baht","doi":"10.1093/jbmrpl/ziae023","DOIUrl":"10.1093/jbmrpl/ziae023","url":null,"abstract":"<p><p>Inflammation is thought to be dysregulated with age leading to impaired bone fracture healing. However, broad analyses of inflammatory processes during homeostatic bone aging and during repair are lacking. Here, we assessed changes in inflammatory cell and cytokine profiles in circulation and in bone tissue to identify age- and sex-dependent differences during homeostasis and repair. During homeostatic aging, male mice demonstrated accumulation of CD4+ helper T cells and CD8+ cytotoxic T cells within bone while both pro-inflammatory \"M1\" and anti-inflammatory \"M2\" macrophage numbers decreased. Female mice saw no age-associated changes in immune-cell population in homeostatic bone. Concentrations of IL-1β, IL-9, IFNγ, and CCL3/MIP-1α increased with age in both male and female mice, whereas concentrations of IL-2, TNFα, TNFR1, IL-4, and IL-10 increased only in female mice - thus we termed these \"age-accumulated\" cytokines. There were no notable changes in immune cell populations nor cytokines within circulation during aging. Sex-dependent analysis demonstrated slight changes in immune cell and cytokine levels within bone and circulation, which were lost upon fracture injury. Fracture in young male mice caused a sharp decrease in number of M1 macrophages; however, this was not seen in aged male mice nor in female mice of any age. Injury itself induced a decrease in the number of CD8+ T cells within the local tissue of aged male and of female mice but not of young mice. Cytokine analysis of fractured mice revealed that age-accumulated cytokines quickly dissipated after fracture injury, and did not re-accumulate in newly regenerated tissue. Conversely, CXCL1/KC-GRO, CXCL2/MIP-2, IL-6, and CCL2/MCP-1 acted as \"fracture response\" cytokines: increasing sharply after fracture, eventually returning to baseline. Collectively, we classify measured cytokines into three groups: (1) age-accumulated cytokines, (2) female-specific age-accumulated cytokines, and (3) fracture response cytokines. These inflammatory molecules represent potential points of intervention to improve fracture healing outcome.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-02-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10978063/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335594","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":"Multi-scale cortical bone traits vary in females and males from two mouse models of genetic diversity","authors":"Nicole Migotsky, Surabhi Kumar, John T. Shuster, Jennifer C. Coulombe, Bhavya Senwar, Adrian A. Gestos, Charles R Farber, Virginia L Ferguson, Matthew J Silva","doi":"10.1093/jbmrpl/ziae019","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae019","url":null,"abstract":"\u0000 Understanding the genetic basis of cortical bone traits can allow for the discovery of novel genes or biological pathways regulating bone health. Mice are the most widely used mammalian model for skeletal biology and allow for the quantification of traits that can’t easily be evaluated in humans, such as osteocyte lacunar morphology. The goal of our study was to investigate the effect of genetic diversity on multi-scale cortical bone traits of three long bones in skeletally-mature mice. We measured bone morphology, mechanical properties, material properties, lacunar morphology, and mineral composition of mouse bones from two populations of genetic diversity. Additionally, we compared how intra-bone relationships varied in the two populations. Our first population of genetic diversity included 72 females and 72 males from the eight Inbred Founder strains used to create the Diversity Outbred (DO) population. These eight strains together span almost 90% of the genetic diversity found in mice (Mus musculus). Our second population of genetic diversity included 25 genetically unique, outbred females and 25 males from the DO population. We show that multi-scale cortical bone traits vary significantly with genetic background; heritability values range from 21% to 99% indicating genetic control of bone traits across length scales. We show for the first time that lacunar shape and number are highly heritable. Comparing the two populations of genetic diversity, we show each DO mouse does not resemble a single Inbred Founder, but instead the outbred mice display hybrid phenotypes with the elimination of extreme values. Additionally, intra-bone relationships (e.g., ultimate force vs. cortical area) were mainly conserved in our two populations. Overall, this work supports future use of these genetically diverse populations to discover novel genes contributing to cortical bone traits, especially at the lacunar length scale.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140443617","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"It isn’t “just a fracture”","authors":"P. Cawthon, Matthew Drake","doi":"10.1093/jbmrpl/ziae022","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae022","url":null,"abstract":"\u0000 In their recent population-based study of nearly 100 000 patients from Ontario, Canada who had suffered a fracture, Vincent and colleagues characterized post-fracture survival rates. Their findings showed that overall survival was decreased particularly following fractures of the hip or vertebrae, and was worse in men and the oldest old. They found that relative survival, particularly after hip fracture, is strikingly poor with less than one-third of men and one-half of women surviving for 5 years following hip fracture, survival which was far less than that seen for patients afflicted by both prostate and breast cancers. Importantly, mortality risk increased immediately after fracture occurrence and was highest within one month of fracture. Collectively, their data suggest that a short, critical window may exist immediately following fracture in which application of interventions to improve survival is likely to be of greatest value. Future work is urgently needed to identify the best approaches to employ during this critical time period in order to optimize survival in patients who have suffered a fracture.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140443896","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fructooligosaccharides act on the gut-bone axis to improve bone independent of Tregs and alter osteocytes in young adult C57BL/6 female mice.","authors":"Proapa Islam, John A Ice, Sanmi E Alake, Pelumi Adedigba, Bethany Hatter, Kara Robinson, Stephen L Clarke, Ashlee N Ford Versypt, Jerry Ritchey, Edralin A Lucas, Brenda J Smith","doi":"10.1093/jbmrpl/ziae021","DOIUrl":"10.1093/jbmrpl/ziae021","url":null,"abstract":"<p><p>Targeting the gut-bone axis with probiotics and prebiotics is considered as a promising strategy to reduce the risk of osteoporosis. Gut-derived short chain fatty acids (SCFA) mediate the effects of probiotics on bone via Tregs, but it is not known whether prebiotics act through a similar mechanism. We investigated how 2 different prebiotics, tart cherry (TC) and fructooligosaccharide (FOS), affect bone, and whether Tregs are required for this response. Eight-wk-old C57BL/6 female mice were fed with diets supplemented with 10% w/w TC, FOS, or a control diet (Con; AIN-93M) diet, and they received an isotype control or CD25 Ab to suppress Tregs. The FOS diet increased BMC, density, and trabecular bone volume in the vertebra (~40%) and proximal tibia (~30%) compared to the TC and control diets (Con), irrespective of CD25 treatment. Both prebiotics increased (<i>P <</i> .01) fecal SCFAs, but the response was greater with FOS. To determine how FOS affected bone cells, we examined genes involved in osteoblast and osteoclast differentiation and activity as well as genes expressed by osteocytes. The FOS increased the expression of regulators of osteoblast differentiation (bone morphogenetic protein 2 [Bmp2], Wnt family member 10b [Wnt10b] and Osterix [Osx]) and type 1 collagen). Osteoclasts regulators were unaltered. The FOS also increased the expression of genes associated with osteocytes, including (Phex), matrix extracellular phosphoglycoprotein (Mepe), and dentin matrix acidic phosphoprotein 1 (Dmp-1). However, <i>Sost</i>, the gene that encodes for sclerostin was also increased by FOS as the number and density of osteocytes increased. These findings demonstrate that FOS has a greater effect on the bone mass and structure in young adult female mice than TC and that its influence on osteoblasts and osteocytes is not dependent on Tregs.</p>","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-02-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10982850/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140335593","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":"Giant cell arteritis associated with intravenous zoledronic acid administration","authors":"M. L. Balbach, Jennifer R Hewlett, R. Wermers, K. Warrington, S. B. Tanner, Erin Y Chew","doi":"10.1093/jbmrpl/ziae015","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae015","url":null,"abstract":"\u0000 Bisphosphonates frequently provoke a cytokine-driven acute clinical response (ACR) characterized by fever, chills, arthralgias, and myalgias. More rarely an association between aminobisphosphonates, such as alendronate and zoledronic acid, and rheumatologic and/or immune-mediated syndromes (RIMS) has been described. Herein we report two patients, one with a prior history of rheumatic disease and one without, who developed giant cell arteritis meeting the American College of Rheumatology 2022 criteria following zoledronic acid infusion. We subsequently review existing mechanistic and clinical literature supporting this link. The duration of symptoms and elevation of inflammatory markers may serve as indicators for differentiating between the more common ACR and less frequent but potentially morbid RIMS. Although the benefit of bisphosphonates will outweigh the risk of RIMS for most patients with high fracture risk, clinicians should be aware of this phenomenon to assist earlier diagnosis and treatment in affected individuals.","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139963536","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Romosozumab added to ongoing denosumab in postmenopausal osteoporosis, a prospective observational study","authors":"G. Adami, Elisa Pedrollo, Maurizio Rossini, A. Fassio, V. Braga, Emma Pasetto, Francesco Pollastri, C. Benini, O. Viapiana, Davide Gatti","doi":"10.1093/jbmrpl/ziae016","DOIUrl":"https://doi.org/10.1093/jbmrpl/ziae016","url":null,"abstract":"\u0000 \u0000 \u0000 Optimization of sequential and combination treatment is crucial in shaping long-term management of postmenopausal osteoporosis (OP).\u0000 \u0000 \u0000 \u0000 We conducted a 6-month prospective observational study on postmenopausal women with severe OP receiving treatment with romosozumab either alone (in patients naïve to treatment) or in combination with ongoing long-term denosumab (>2 years) or continuing ongoing denosumab alone (>2 years). We collected serum samples for bone turnover markers, bone modulators and calcium phosphate metabolism at baseline, month 3 and month 6. Bone mineral density was assessed at baseline and after 6 months.\u0000 \u0000 \u0000 \u0000 Fifty-two postmenopausal women with OP were included in the study. Nineteen received romosozumab alone, 11 received romosozumab combined to ongoing denosumab and 22 continued denosumab alone. BMD increased significantly at all sites at 6 months of follow-up in the romosozumab alone group (femoral neck +8.1%, total hip +6.8% and lumbar spine +7.9%). In contrast, BMD increased significantly only at lumbar spine in the combination group (+7.2%) and in the denosumab group (+1.5%). P1nP increased significantly in romosozumab groups at month 3 (+70.4% in romosozumab alone group and + 99.1% in combination group). Sclerostin levels increased steeply in both romosozumab groups and Dkk1 did not change.\u0000 \u0000 \u0000 \u0000 Romosozumab added to ongoing denosumab resulted in an increase in P1nP and lumbar spine BMD, but not in femoral neck BMD. For patients on denosumab, using romosozumab as an additional treatment appeared to be useful in terms of bone formation markers and spine BMD versus denosumab alone. Further randomized controlled trials, possibly powered to fracture outcomes, are needed to confirm our results.\u0000","PeriodicalId":14611,"journal":{"name":"JBMR Plus","volume":null,"pages":null},"PeriodicalIF":3.8,"publicationDate":"2024-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139797170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}