Bone Research最新文献

{"title":"Small-molecule amines: a big role in the regulation of bone homeostasis.","authors":"Qian Zhang,&nbsp;Jirong Yang,&nbsp;Nan Hu,&nbsp;Juan Liu,&nbsp;Huan Yu,&nbsp;Haobo Pan,&nbsp;Di Chen,&nbsp;Changshun Ruan","doi":"10.1038/s41413-023-00262-z","DOIUrl":"https://doi.org/10.1038/s41413-023-00262-z","url":null,"abstract":"<p><p>Numerous small-molecule amines (SMAs) play critical roles in maintaining bone homeostasis and promoting bone regeneration regardless of whether they are applied as drugs or biomaterials. On the one hand, SMAs promote bone formation or inhibit bone resorption through the regulation of key molecular signaling pathways in osteoblasts/osteoclasts; on the other hand, owing to their alkaline properties as well as their antioxidant and anti-inflammatory features, most SMAs create a favorable microenvironment for bone homeostasis. However, due to a lack of information on their structure/bioactivity and underlying mechanisms of action, certain SMAs cannot be developed into drugs or biomaterials for bone disease treatment. In this review, we thoroughly summarize the current understanding of SMA effects on bone homeostasis, including descriptions of their classifications, biochemical features, recent research advances in bone biology and related regulatory mechanisms in bone regeneration. In addition, we discuss the challenges and prospects of SMA translational research.</p>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2023-07-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10363555/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9860856","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Tppp3⁺ synovial/tendon sheath progenitor cells contribute to heterotopic bone after trauma.","authors":"Ji-Hye Yea, Mario Gomez-Salazar, Sharon Onggo, Zhao Li, Neelima Thottappillil, Masnsen Cherief, Stefano Negri, Xin Xing, Qizhi Qin, Robert Joel Tower, Chen-Ming Fan, Benjamin Levi, Aaron W James","doi":"10.1038/s41413-023-00272-x","DOIUrl":"10.1038/s41413-023-00272-x","url":null,"abstract":"<p><p>Heterotopic ossification (HO) is a pathological process resulting in aberrant bone formation and often involves synovial lined tissues. During this process, mesenchymal progenitor cells undergo endochondral ossification. Nonetheless, the specific cell phenotypes and mechanisms driving this process are not well understood, in part due to the high degree of heterogeneity of the progenitor cells involved. Here, using a combination of lineage tracing and single-cell RNA sequencing (scRNA-seq), we investigated the extent to which synovial/tendon sheath progenitor cells contribute to heterotopic bone formation. For this purpose, Tppp3 (tubulin polymerization-promoting protein family member 3)-inducible reporter mice were used in combination with either Scx (Scleraxis) or Pdgfra (platelet derived growth factor receptor alpha) reporter mice. Both tendon injury- and arthroplasty-induced mouse experimental HO models were utilized. ScRNA-seq of tendon-associated traumatic HO suggested that Tppp3 is an early progenitor cell marker for either tendon or osteochondral cells. Upon HO induction, Tppp3 reporter⁺ cells expanded in number and partially contributed to cartilage and bone formation in either tendon- or joint-associated HO. In double reporter animals, both Pdgfra⁺Tppp3⁺ and Pdgfra⁺Tppp3^- progenitor cells gave rise to HO-associated cartilage. Finally, analysis of human samples showed a substantial population of TPPP3-expressing cells overlapping with osteogenic markers in areas of heterotopic bone. Overall, these data demonstrate that synovial/tendon sheath progenitor cells undergo aberrant osteochondral differentiation and contribute to HO after trauma.</p>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2023-07-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10361999/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10220805","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Correction: mTORC1 induces plasma membrane depolarization and promotes preosteoblast senescence through regulating the sodium channel Scn1a.","authors":"Ajuan Chen,&nbsp;Jian Jin,&nbsp;Shasha Cheng,&nbsp;Zezheng Liu,&nbsp;Cheng Yang,&nbsp;Qingjing Chen,&nbsp;Wenquan Liang,&nbsp;Kai Li,&nbsp;Dawei Kang,&nbsp;Zhicong Ouyang,&nbsp;Chenfeng Yao,&nbsp;Xiaochun Bai,&nbsp;Qingchu Li,&nbsp;Dadi Jin,&nbsp;Bin Huang","doi":"10.1038/s41413-023-00276-7","DOIUrl":"https://doi.org/10.1038/s41413-023-00276-7","url":null,"abstract":"","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2023-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10359267/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9855214","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Causal associations of brain structure with bone mineral density: a large-scale genetic correlation study.","authors":"Bin Guo, Chao Wang, Yong Zhu, Zhi Liu, Haitao Long, Zhe Ruan, Zhangyuan Lin, Zhihua Fan, Yusheng Li, Shushan Zhao","doi":"10.1038/s41413-023-00270-z","DOIUrl":"10.1038/s41413-023-00270-z","url":null,"abstract":"<p><p>In this study, we aimed to investigate the causal associations of brain structure with bone mineral density (BMD). Based on the genome-wide association study (GWAS) summary statistics of 1 325 brain imaging-derived phenotypes (BIDPs) of brain structure from the UK Biobank and GWAS summary datasets of 5 BMD locations, including the total body, femoral neck, lumbar spine, forearm, and heel from the GEFOS Consortium, linkage disequilibrium score regression (LDSC) was conducted to determine the genetic correlations, and Mendelian randomization (MR) was then performed to explore the causal relationship between the BIDPs and BMD. Several sensitivity analyses were performed to verify the strength and stability of the present MR outcomes. To increase confidence in our findings, we also performed confirmatory MR between BIDPs and osteoporosis. LDSC revealed that 1.93% of BIDPs, with a false discovery rate (FDR) < 0.01, were genetically correlated with BMD. Additionally, we observed that 1.31% of BIDPs exhibited a significant causal relationship with BMD (FDR < 0.01) through MR. Both the LDSC and MR results demonstrated that the BIDPs \"Volume of normalized brain,\" \"Volume of gray matter in Left Inferior Frontal Gyrus, pars opercularis,\" \"Volume of Estimated Total Intra Cranial\" and \"Volume-ratio of brain segmentation/estimated total intracranial\" had strong associations with BMD. Interestingly, our results showed that more left BIDPs were causally associated with BMD, especially within and around the left frontal region. In conclusion, a part of the brain structure causally influences BMD, which may provide important perspectives for the prevention of osteoporosis and offer valuable insights for further research on the brain-bone axis.</p>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2023-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10359275/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10234092","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Glucose uptake and distribution across the human skeleton using state-of-the-art total-body PET/CT.","authors":"Weizhao Lu,&nbsp;Yanhua Duan,&nbsp;Kun Li,&nbsp;Jianfeng Qiu,&nbsp;Zhaoping Cheng","doi":"10.1038/s41413-023-00268-7","DOIUrl":"https://doi.org/10.1038/s41413-023-00268-7","url":null,"abstract":"<p><p>A growing number of studies have demonstrated that the skeleton is an endocrine organ that is involved in glucose metabolism and plays a significant role in human glucose homeostasis. However, there is still a limited understanding of the in vivo glucose uptake and distribution across the human skeleton. To address this issue, we aimed to elucidate the detailed profile of glucose uptake across the skeleton using a total-body positron emission tomography (PET) scanner. A total of 41 healthy participants were recruited. Two of them received a 1-hour dynamic total-body ¹⁸F-fluorodeoxyglucose (¹⁸F-FDG) PET scan, and all of them received a 10-minute static total-body ¹⁸F-FDG PET scan. The net influx rate (K_i) and standardized uptake value normalized by lean body mass (SUL) were calculated as indicators of glucose uptake from the dynamic and static PET data, respectively. The results showed that the vertebrae, hip bone and skull had relatively high K_i and SUL values compared with metabolic organs such as the liver. Both the K_i and SUL were higher in the epiphyseal, metaphyseal and cortical regions of long bones. Moreover, trends associated with age and overweight with glucose uptake (SUL_max and SUL_mean) in bones were uncovered. Overall, these results indicate that the skeleton is a site with significant glucose uptake, and skeletal glucose uptake can be affected by age and dysregulated metabolism.</p>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2023-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10322940/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9802831","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Premature aging of skeletal stem/progenitor cells rather than osteoblasts causes bone loss with decreased mechanosensation.","authors":"Ruici Yang,&nbsp;Dandan Cao,&nbsp;Jinlong Suo,&nbsp;Lingli Zhang,&nbsp;Chunyang Mo,&nbsp;Miaomiao Wang,&nbsp;Ningning Niu,&nbsp;Rui Yue,&nbsp;Weiguo Zou","doi":"10.1038/s41413-023-00269-6","DOIUrl":"https://doi.org/10.1038/s41413-023-00269-6","url":null,"abstract":"<p><p>A distinct population of skeletal stem/progenitor cells (SSPCs) has been identified that is indispensable for the maintenance and remodeling of the adult skeleton. However, the cell types that are responsible for age-related bone loss and the characteristic changes in these cells during aging remain to be determined. Here, we established models of premature aging by conditional depletion of Zmpste24 (Z24) in mice and found that Prx1-dependent Z24 deletion, but not Osx-dependent Z24 deletion, caused significant bone loss. However, Acan-associated Z24 depletion caused only trabecular bone loss. Single-cell RNA sequencing (scRNA-seq) revealed that two populations of SSPCs, one that differentiates into trabecular bone cells and another that differentiates into cortical bone cells, were significantly decreased in Prx1-Cre; Z24^f/f mice. Both premature SSPC populations exhibited apoptotic signaling pathway activation and decreased mechanosensation. Physical exercise reversed the effects of Z24 depletion on cellular apoptosis, extracellular matrix expression and bone mass. This study identified two populations of SSPCs that are responsible for premature aging-related bone loss. The impairment of mechanosensation in Z24-deficient SSPCs provides new insight into how physical exercise can be used to prevent bone aging.</p>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2023-07-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10322990/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9804170","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"A novel multifunctional radioprotective strategy using P7C3 as a countermeasure against ionizing radiation-induced bone loss.","authors":"Fei Wei,&nbsp;Zewen Kelvin Tuong,&nbsp;Mahmoud Omer,&nbsp;Christopher Ngo,&nbsp;Jackson Asiatico,&nbsp;Michael Kinzel,&nbsp;Abinaya Sindu Pugazhendhi,&nbsp;Annette R Khaled,&nbsp;Ranajay Ghosh,&nbsp;Melanie Coathup","doi":"10.1038/s41413-023-00273-w","DOIUrl":"https://doi.org/10.1038/s41413-023-00273-w","url":null,"abstract":"<p><p>Radiotherapy is a critical component of cancer care but can cause osteoporosis and pathological insufficiency fractures in surrounding and otherwise healthy bone. Presently, no effective countermeasure exists, and ionizing radiation-induced bone damage continues to be a substantial source of pain and morbidity. The purpose of this study was to investigate a small molecule aminopropyl carbazole named P7C3 as a novel radioprotective strategy. Our studies revealed that P7C3 repressed ionizing radiation (IR)-induced osteoclastic activity, inhibited adipogenesis, and promoted osteoblastogenesis and mineral deposition in vitro. We also demonstrated that rodents exposed to clinically equivalent hypofractionated levels of IR in vivo develop weakened, osteoporotic bone. However, the administration of P7C3 significantly inhibited osteoclastic activity, lipid formation and bone marrow adiposity and mitigated tissue loss such that bone maintained its area, architecture, and mechanical strength. Our findings revealed significant enhancement of cellular macromolecule metabolic processes, myeloid cell differentiation, and the proteins LRP-4, TAGLN, ILK, and Tollip, with downregulation of GDF-3, SH2B1, and CD200. These proteins are key in favoring osteoblast over adipogenic progenitor differentiation, cell matrix interactions, and shape and motility, facilitating inflammatory resolution, and suppressing osteoclastogenesis, potentially via Wnt/β-catenin signaling. A concern was whether P7C3 afforded similar protection to cancer cells. Preliminarily, and remarkably, at the same protective P7C3 dose, a significant reduction in triple-negative breast cancer and osteosarcoma cell metabolic activity was found in vitro. Together, these results indicate that P7C3 is a previously undiscovered key regulator of adipo-osteogenic progenitor lineage commitment and may serve as a novel multifunctional therapeutic strategy, leaving IR an effective clinical tool while diminishing the risk of adverse post-IR complications. Our data uncover a new approach for the prevention of radiation-induced bone damage, and further work is needed to investigate its ability to selectively drive cancer cell death.</p>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2023-06-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10310858/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9746498","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author Correction: Super enhancers targeting ZBTB16 in osteogenesis protect against osteoporosis.","authors":"Wenhui Yu,&nbsp;Zhongyu Xie,&nbsp;Jinteng Li,&nbsp;Jiajie Lin,&nbsp;Zepeng Su,&nbsp;Yunshu Che,&nbsp;Feng Ye,&nbsp;Zhaoqiang Zhang,&nbsp;Peitao Xu,&nbsp;Yipeng Zeng,&nbsp;Xiaojun Xu,&nbsp;Zhikun Li,&nbsp;Pei Feng,&nbsp;Rujia Mi,&nbsp;Yanfeng Wu,&nbsp;Huiyong Shen","doi":"10.1038/s41413-023-00275-8","DOIUrl":"https://doi.org/10.1038/s41413-023-00275-8","url":null,"abstract":"","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2023-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10293191/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9716073","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Author Correction: Reversal of the diabetic bone signature with anabolic therapies in mice.","authors":"Silvia Marino,&nbsp;Nisreen Akel,&nbsp;Shenyang Li,&nbsp;Meloney Cregor,&nbsp;Meghan Jones,&nbsp;Betiana Perez,&nbsp;Gaston Troncoso,&nbsp;Jomeeka Meeks,&nbsp;Scott Stewart,&nbsp;Amy Y Sato,&nbsp;Intawat Nookaew,&nbsp;Teresita Bellido","doi":"10.1038/s41413-023-00274-9","DOIUrl":"https://doi.org/10.1038/s41413-023-00274-9","url":null,"abstract":"","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2023-06-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10264430/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9639373","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Modulation of bone remodeling by the gut microbiota: a new therapy for osteoporosis.","authors":"Zhengtian Lyu, Yongfei Hu, Yuming Guo, Dan Liu","doi":"10.1038/s41413-023-00264-x","DOIUrl":"10.1038/s41413-023-00264-x","url":null,"abstract":"<p><p>The gut microbiota (GM) plays a crucial role in maintaining the overall health and well-being of the host. Recent studies have demonstrated that the GM may significantly influence bone metabolism and degenerative skeletal diseases, such as osteoporosis (OP). Interventions targeting GM modification, including probiotics or antibiotics, have been found to affect bone remodeling. This review provides a comprehensive summary of recent research on the role of GM in regulating bone remodeling and seeks to elucidate the regulatory mechanism from various perspectives, such as the interaction with the immune system, interplay with estrogen or parathyroid hormone (PTH), the impact of GM metabolites, and the effect of extracellular vesicles (EVs). Moreover, this review explores the potential of probiotics as a therapeutic approach for OP. The insights presented may contribute to the development of innovative GM-targeted therapies for OP.</p>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":null,"pages":null},"PeriodicalIF":14.3,"publicationDate":"2023-06-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10256815/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9610899","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}