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A new perspective on intervertebral disc calcification—from bench to bedside 椎间盘钙化的新视角--从工作台到床边
IF 12.7 1区 医学
Bone Research Pub Date : 2024-01-22 DOI: 10.1038/s41413-023-00307-3
Emanuel J. Novais, Rajkishen Narayanan, Jose A. Canseco, Koen van de Wetering, Christopher K. Kepler, Alan S. Hilibrand, Alexander R. Vaccaro, Makarand V. Risbud
{"title":"A new perspective on intervertebral disc calcification—from bench to bedside","authors":"Emanuel J. Novais, Rajkishen Narayanan, Jose A. Canseco, Koen van de Wetering, Christopher K. Kepler, Alan S. Hilibrand, Alexander R. Vaccaro, Makarand V. Risbud","doi":"10.1038/s41413-023-00307-3","DOIUrl":"https://doi.org/10.1038/s41413-023-00307-3","url":null,"abstract":"<p>Disc degeneration primarily contributes to chronic low back and neck pain. Consequently, there is an urgent need to understand the spectrum of disc degeneration phenotypes such as fibrosis, ectopic calcification, herniation, or mixed phenotypes. Amongst these phenotypes, disc calcification is the least studied. Ectopic calcification, by definition, is the pathological mineralization of soft tissues, widely studied in the context of conditions that afflict vasculature, skin, and cartilage. Clinically, disc calcification is associated with poor surgical outcomes and back pain refractory to conservative treatment. It is frequently seen as a consequence of disc aging and progressive degeneration but exhibits unique molecular and morphological characteristics: hypertrophic chondrocyte-like cell differentiation; TNAP, ENPP1, and ANK upregulation; cell death; altered Pi and PPi homeostasis; and local inflammation. Recent studies in mouse models have provided a better understanding of the mechanisms underlying this phenotype. It is essential to recognize that the presentation and nature of mineralization differ between AF, NP, and EP compartments. Moreover, the combination of anatomic location, genetics, and environmental stressors, such as aging or trauma, govern the predisposition to calcification. Lastly, the systemic regulation of calcium and Pi metabolism is less important than the local activity of PPi modulated by the ANK-ENPP1 axis, along with disc cell death and differentiation status. While there is limited understanding of this phenotype, understanding the molecular pathways governing local intervertebral disc calcification may lead to developing disease-modifying drugs and better clinical management of degeneration-related pathologies.</p>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2024-01-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139510784","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
MicroRNA-146a-loaded magnesium silicate nanospheres promote bone regeneration in an inflammatory microenvironment. 微RNA-146a负载硅酸镁纳米球促进炎症微环境中的骨再生
IF 12.7 1区 医学
Bone Research Pub Date : 2024-01-15 DOI: 10.1038/s41413-023-00299-0
Jiakang Yang, Jing Shuai, Lixuen Siow, Jingyi Lu, Miao Sun, Wenyue An, Mengfei Yu, Baixiang Wang, Qianming Chen
{"title":"MicroRNA-146a-loaded magnesium silicate nanospheres promote bone regeneration in an inflammatory microenvironment.","authors":"Jiakang Yang, Jing Shuai, Lixuen Siow, Jingyi Lu, Miao Sun, Wenyue An, Mengfei Yu, Baixiang Wang, Qianming Chen","doi":"10.1038/s41413-023-00299-0","DOIUrl":"10.1038/s41413-023-00299-0","url":null,"abstract":"<p><p>Reconstruction of irregular oral-maxillofacial bone defects with an inflammatory microenvironment remains a challenge, as chronic local inflammation can largely impair bone healing. Here, we used magnesium silicate nanospheres (MSNs) to load microRNA-146a-5p (miR-146a) to fabricate a nanobiomaterial, MSN+miR-146a, which showed synergistic promoting effects on the osteogenic differentiation of human dental pulp stem cells (hDPSCs). In addition, miR-146a exhibited an anti-inflammatory effect on mouse bone marrow-derived macrophages (BMMs) under lipopolysaccharide (LPS) stimulation by inhibiting the NF-κB pathway via targeting tumor necrosis factor receptor-associated factor 6 (TRAF6), and MSNs could simultaneously promote M2 polarization of BMMs. MiR-146a was also found to inhibit osteoclast formation. Finally, the dual osteogenic-promoting and immunoregulatory effects of MSN+miR-146a were further validated in a stimulated infected mouse mandibular bone defect model via delivery by a photocuring hydrogel. Collectively, the MSN+miR-146a complex revealed good potential in treating inflammatory irregular oral-maxillofacial bone defects.</p>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2024-01-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10788347/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139467044","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}
引用次数: 0
Estradiol increases cortical and trabecular bone accrual and bone strength in an adolescent male-to-female mouse model of gender-affirming hormone therapy 雌二醇可增加青少年雄性变雌性小鼠性别确认激素疗法模型的皮质骨和骨小梁增生以及骨强度
IF 12.7 1区 医学
Bone Research Pub Date : 2024-01-11 DOI: 10.1038/s41413-023-00308-2
Tian Nie, Varun S. Venkatesh, Suzanne Golub, Kathryn S. Stok, Haniyeh Hemmatian, Reena Desai, David J. Handelsman, Jeffrey D. Zajac, Mathis Grossmann, Rachel A. Davey
{"title":"Estradiol increases cortical and trabecular bone accrual and bone strength in an adolescent male-to-female mouse model of gender-affirming hormone therapy","authors":"Tian Nie, Varun S. Venkatesh, Suzanne Golub, Kathryn S. Stok, Haniyeh Hemmatian, Reena Desai, David J. Handelsman, Jeffrey D. Zajac, Mathis Grossmann, Rachel A. Davey","doi":"10.1038/s41413-023-00308-2","DOIUrl":"https://doi.org/10.1038/s41413-023-00308-2","url":null,"abstract":"<p>The effects of gender-affirming hormone therapy on the skeletal integrity and fracture risk in transitioning adolescent trans girls are unknown. To address this knowledge gap, we developed a mouse model to simulate male-to-female transition in human adolescents in whom puberty is first arrested by using gonadotrophin-releasing hormone analogs with subsequent estradiol treatment. Puberty was suppressed by orchidectomy in male mice at 5 weeks of age. At 3 weeks post-surgery, male-to-female mice were treated with a high dose of estradiol (~0.85 mg) by intraperitoneal silastic implantation for 12 weeks. Controls included intact and orchidectomized males at 3 weeks post-surgery, vehicle-treated intact males, intact females and orchidectomized males at 12 weeks post-treatment. Compared to male controls, orchidectomized males exhibited decreased peak bone mass accrual and a decreased maximal force the bone could withstand prior to fracture. Estradiol treatment in orchidectomized male-to-female mice compared to mice in all control groups was associated with an increased cortical thickness in the mid-diaphysis, while the periosteal circumference increased to a level that was intermediate between intact male and female controls, resulting in increased maximal force and stiffness. In trabecular bone, estradiol treatment increased newly formed trabeculae arising from the growth plate as well as mineralizing surface/bone surface and bone formation rate, consistent with the anabolic action of estradiol on osteoblast proliferation. These data support the concept that skeletal integrity can be preserved and that long-term fractures may be prevented in trans girls treated with GnRHa and a sufficiently high dose of GAHT. Further study is needed to identify an optimal dose of estradiol that protects the bone without adverse side effects.</p>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2024-01-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"139419996","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Neuro–bone tissue engineering: emerging mechanisms, potential strategies, and current challenges 神经骨组织工程:新兴机制、潜在战略和当前挑战
IF 12.7 1区 医学
Bone Research Pub Date : 2023-12-20 DOI: 10.1038/s41413-023-00302-8
Wenzhe Sun, Bing Ye, Siyue Chen, Lian Zeng, Hongwei Lu, Yizhou Wan, Qing Gao, Kaifang Chen, Yanzhen Qu, Bin Wu, Xiao Lv, Xiaodong Guo
{"title":"Neuro–bone tissue engineering: emerging mechanisms, potential strategies, and current challenges","authors":"Wenzhe Sun, Bing Ye, Siyue Chen, Lian Zeng, Hongwei Lu, Yizhou Wan, Qing Gao, Kaifang Chen, Yanzhen Qu, Bin Wu, Xiao Lv, Xiaodong Guo","doi":"10.1038/s41413-023-00302-8","DOIUrl":"https://doi.org/10.1038/s41413-023-00302-8","url":null,"abstract":"<p>The skeleton is a highly innervated organ in which nerve fibers interact with various skeletal cells. Peripheral nerve endings release neurogenic factors and sense skeletal signals, which mediate bone metabolism and skeletal pain. In recent years, bone tissue engineering has increasingly focused on the effects of the nervous system on bone regeneration. Simultaneous regeneration of bone and nerves through the use of materials or by the enhancement of endogenous neurogenic repair signals has been proven to promote functional bone regeneration. Additionally, emerging information on the mechanisms of skeletal interoception and the central nervous system regulation of bone homeostasis provide an opportunity for advancing biomaterials. However, comprehensive reviews of this topic are lacking. Therefore, this review provides an overview of the relationship between nerves and bone regeneration, focusing on tissue engineering applications. We discuss novel regulatory mechanisms and explore innovative approaches based on nerve–bone interactions for bone regeneration. Finally, the challenges and future prospects of this field are briefly discussed.</p>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2023-12-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138770763","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Sensory nerves directly promote osteoclastogenesis by secreting peptidyl-prolyl cis-trans isomerase D (Cyp40) 感觉神经通过分泌肽基脯氨酰顺反异构酶 D(Cyp40)直接促进破骨细胞生成
IF 12.7 1区 医学
Bone Research Pub Date : 2023-12-14 DOI: 10.1038/s41413-023-00300-w
Junqin Li, Bin Liu, Hao Wu, Shuaishuai Zhang, Zhuowen Liang, Shuo Guo, Huijie Jiang, Yue Song, Xing Lei, Yi Gao, Pengzhen Cheng, Donglin Li, Jimeng Wang, Yang Liu, Di Wang, Nazhi Zhan, Jing Xu, Lin Wang, Guozhi Xiao, Liu Yang, GuoXian Pei
{"title":"Sensory nerves directly promote osteoclastogenesis by secreting peptidyl-prolyl cis-trans isomerase D (Cyp40)","authors":"Junqin Li, Bin Liu, Hao Wu, Shuaishuai Zhang, Zhuowen Liang, Shuo Guo, Huijie Jiang, Yue Song, Xing Lei, Yi Gao, Pengzhen Cheng, Donglin Li, Jimeng Wang, Yang Liu, Di Wang, Nazhi Zhan, Jing Xu, Lin Wang, Guozhi Xiao, Liu Yang, GuoXian Pei","doi":"10.1038/s41413-023-00300-w","DOIUrl":"https://doi.org/10.1038/s41413-023-00300-w","url":null,"abstract":"<p>Given afferent functions, sensory nerves have recently been found to exert efferent effects and directly alter organ physiology. Additionally, several studies have highlighted the indirect but crucial role of sensory nerves in the regulation of the physiological function of osteoclasts. Nonetheless, evidence regarding the direct sensory nerve efferent influence on osteoclasts is lacking. In the current study, we found that high levels of efferent signals were transported directly from the sensory nerves into osteoclasts. Furthermore, sensory hypersensitivity significantly increased osteoclastic bone resorption, and sensory neurons (SNs) directly promoted osteoclastogenesis in an in vitro coculture system. Moreover, we screened a novel neuropeptide, Cyp40, using an isobaric tag for relative and absolute quantitation (iTRAQ). We observed that Cyp40 is the efferent signal from sensory nerves, and it plays a critical role in osteoclastogenesis via the aryl hydrocarbon receptor (AhR)-Ras/Raf-p-Erk-NFATc1 pathway. These findings revealed a novel mechanism regarding the influence of sensory nerves on bone regulation, i.e., a direct promoting effect on osteoclastogenesis by the secretion of Cyp40. Therefore, inhibiting Cyp40 could serve as a strategy to improve bone quality in osteoporosis and promote bone repair after bone injury.</p>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2023-12-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138582810","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Risk of metabolic abnormalities in osteoarthritis: a new perspective to understand its pathological mechanisms. 骨关节炎代谢异常的风险:了解其病理机制的新视角。
IF 12.7 1区 医学
Bone Research Pub Date : 2023-12-06 DOI: 10.1038/s41413-023-00301-9
Guizheng Wei, Ke Lu, Muhammad Umar, Zhenglin Zhu, William W Lu, John R Speakman, Yan Chen, Liping Tong, Di Chen
{"title":"Risk of metabolic abnormalities in osteoarthritis: a new perspective to understand its pathological mechanisms.","authors":"Guizheng Wei, Ke Lu, Muhammad Umar, Zhenglin Zhu, William W Lu, John R Speakman, Yan Chen, Liping Tong, Di Chen","doi":"10.1038/s41413-023-00301-9","DOIUrl":"10.1038/s41413-023-00301-9","url":null,"abstract":"<p><p>Although aging has traditionally been viewed as the most important risk factor for osteoarthritis (OA), an increasing amount of epidemiological evidence has highlighted the association between metabolic abnormalities and OA, particularly in younger individuals. Metabolic abnormalities, such as obesity and type II diabetes, are strongly linked to OA, and they affect both weight-bearing and non-weight-bearing joints, thus suggesting that the pathogenesis of OA is more complicated than the mechanical stress induced by overweight. This review aims to explore the recent advances in research on the relationship between metabolic abnormalities and OA risk, including the impact of abnormal glucose and lipid metabolism, the potential pathogenesis and targeted therapeutic strategies.</p>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2023-12-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10698167/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138486667","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}
引用次数: 0
Lipolysis supports bone formation by providing osteoblasts with endogenous fatty acid substrates to maintain bioenergetic status. 脂肪分解通过为成骨细胞提供内源性脂肪酸底物来维持生物能量状态,从而支持骨形成。
IF 12.7 1区 医学
Bone Research Pub Date : 2023-11-24 DOI: 10.1038/s41413-023-00297-2
Ananya Nandy, Ron C M Helderman, Santosh Thapa, Shobana Jayapalan, Alison Richards, Nikita Narayani, Michael P Czech, Clifford J Rosen, Elizabeth Rendina-Ruedy
{"title":"Lipolysis supports bone formation by providing osteoblasts with endogenous fatty acid substrates to maintain bioenergetic status.","authors":"Ananya Nandy, Ron C M Helderman, Santosh Thapa, Shobana Jayapalan, Alison Richards, Nikita Narayani, Michael P Czech, Clifford J Rosen, Elizabeth Rendina-Ruedy","doi":"10.1038/s41413-023-00297-2","DOIUrl":"10.1038/s41413-023-00297-2","url":null,"abstract":"<p><p>Bone formation is a highly energy-demanding process that can be impacted by metabolic disorders. Glucose has been considered the principal substrate for osteoblasts, although fatty acids are also important for osteoblast function. Here, we report that osteoblasts can derive energy from endogenous fatty acids stored in lipid droplets via lipolysis and that this process is critical for bone formation. As such, we demonstrate that osteoblasts accumulate lipid droplets that are highly dynamic and provide the molecular mechanism by which they serve as a fuel source for energy generation during osteoblast maturation. Inhibiting cytoplasmic lipolysis leads to both an increase in lipid droplet size in osteoblasts and an impairment in osteoblast function. The fatty acids released by lipolysis from these lipid droplets become critical for cellular energy production as cellular energetics shifts towards oxidative phosphorylation during nutrient-depleted conditions. In vivo, conditional deletion of the ATGL-encoding gene Pnpla2 in osteoblast progenitor cells reduces cortical and trabecular bone parameters and alters skeletal lipid metabolism. Collectively, our data demonstrate that osteoblasts store fatty acids in the form of lipid droplets, which are released via lipolysis to support cellular bioenergetic status when nutrients are limited. Perturbations in this process result in impairment of bone formation, specifically reducing ATP production and overall osteoblast function.</p>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2023-11-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10673934/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138433308","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}
引用次数: 0
Structure and function of the membrane microdomains in osteoclasts. 破骨细胞膜微结构域的结构与功能。
IF 12.7 1区 医学
Bone Research Pub Date : 2023-11-21 DOI: 10.1038/s41413-023-00294-5
Jialong Hou, Jian Liu, Zhixian Huang, Yining Wang, Hanbing Yao, Zhenxin Hu, Chengge Shi, Jiake Xu, Qingqing Wang
{"title":"Structure and function of the membrane microdomains in osteoclasts.","authors":"Jialong Hou, Jian Liu, Zhixian Huang, Yining Wang, Hanbing Yao, Zhenxin Hu, Chengge Shi, Jiake Xu, Qingqing Wang","doi":"10.1038/s41413-023-00294-5","DOIUrl":"10.1038/s41413-023-00294-5","url":null,"abstract":"<p><p>The cell membrane structure is closely related to the occurrence and progression of many metabolic bone diseases observed in the clinic and is an important target to the development of therapeutic strategies for these diseases. Strong experimental evidence supports the existence of membrane microdomains in osteoclasts (OCs). However, the potential membrane microdomains and the crucial mechanisms underlying their roles in OCs have not been fully characterized. Membrane microdomain components, such as scaffolding proteins and the actin cytoskeleton, as well as the roles of individual membrane proteins, need to be elucidated. In this review, we discuss the compositions and critical functions of membrane microdomains that determine the biological behavior of OCs through the three main stages of the OC life cycle.</p>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2023-11-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10663511/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"138290326","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}
引用次数: 0
Annexin A5 derived from matrix vesicles protects against osteoporotic bone loss via mineralization. 来源于基质小泡的膜联蛋白A5通过矿化作用防止骨质疏松性骨丢失。
IF 12.7 1区 医学
Bone Research Pub Date : 2023-11-09 DOI: 10.1038/s41413-023-00290-9
Guanyue Su, Demao Zhang, Tiantian Li, Tong Pei, Jie Yang, Shasha Tu, Sijun Liu, Jie Ren, Yaojia Zhang, Mengmeng Duan, Xinrui Yang, Yang Shen, Chenchen Zhou, Jing Xie, Xiaoheng Liu
{"title":"Annexin A5 derived from matrix vesicles protects against osteoporotic bone loss via mineralization.","authors":"Guanyue Su, Demao Zhang, Tiantian Li, Tong Pei, Jie Yang, Shasha Tu, Sijun Liu, Jie Ren, Yaojia Zhang, Mengmeng Duan, Xinrui Yang, Yang Shen, Chenchen Zhou, Jing Xie, Xiaoheng Liu","doi":"10.1038/s41413-023-00290-9","DOIUrl":"10.1038/s41413-023-00290-9","url":null,"abstract":"<p><p>Matrix vesicles (MVs) have shown strong effects in diseases such as vascular ectopic calcification and pathological calcified osteoarthritis and in wound repair of the skeletal system due to their membranous vesicle characteristics and abundant calcium and phosphorus content. However, the role of MVs in the progression of osteoporosis is poorly understood. Here, we report that annexin A5, an important component of the matrix vesicle membrane, plays a vital role in bone matrix homeostasis in the deterioration of osteoporosis. We first identified annexin A5 from adherent MVs but not dissociative MVs of osteoblasts and found that it could be sharply decreased in the bone matrix during the occurrence of osteoporosis based on ovariectomized mice. We then confirmed its potential in mediating the mineralization of the precursor osteoblast lineage via its initial binding with collagen type I to achieve MV adhesion and the subsequent activation of cellular autophagy. Finally, we proved its protective role in resisting bone loss by applying it to osteoporotic mice. Taken together, these data revealed the importance of annexin A5, originating from adherent MVs of osteoblasts, in bone matrix remodeling of osteoporosis and provided a new strategy for the treatment and intervention of bone loss.</p>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2023-11-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10632518/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71520471","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}
引用次数: 0
Spatial transcriptomic interrogation of the murine bone marrow signaling landscape. 小鼠骨髓信号传导景观的空间转录组学研究。
IF 12.7 1区 医学
Bone Research Pub Date : 2023-11-06 DOI: 10.1038/s41413-023-00298-1
Xue Xiao, Conan Juan, Tingsheng Drennon, Cedric R Uytingco, Neda Vishlaghi, Dimitri Sokolowskei, Lin Xu, Benjamin Levi, Mimi C Sammarco, Robert J Tower
{"title":"Spatial transcriptomic interrogation of the murine bone marrow signaling landscape.","authors":"Xue Xiao, Conan Juan, Tingsheng Drennon, Cedric R Uytingco, Neda Vishlaghi, Dimitri Sokolowskei, Lin Xu, Benjamin Levi, Mimi C Sammarco, Robert J Tower","doi":"10.1038/s41413-023-00298-1","DOIUrl":"10.1038/s41413-023-00298-1","url":null,"abstract":"<p><p>Self-renewal and differentiation of skeletal stem and progenitor cells (SSPCs) are tightly regulated processes, with SSPC dysregulation leading to progressive bone disease. While the application of single-cell RNA sequencing (scRNAseq) to the bone field has led to major advancements in our understanding of SSPC heterogeneity, stem cells are tightly regulated by their neighboring cells which comprise the bone marrow niche. However, unbiased interrogation of these cells at the transcriptional level within their native niche environment has been challenging. Here, we combined spatial transcriptomics and scRNAseq using a predictive modeling pipeline derived from multiple deconvolution packages in adult mouse femurs to provide an endogenous, in vivo context of SSPCs within the niche. This combined approach localized SSPC subtypes to specific regions of the bone and identified cellular components and signaling networks utilized within the niche. Furthermore, the use of spatial transcriptomics allowed us to identify spatially restricted activation of metabolic and major morphogenetic signaling gradients derived from the vasculature and bone surfaces that establish microdomains within the marrow cavity. Overall, we demonstrate, for the first time, the feasibility of applying spatial transcriptomics to fully mineralized tissue and present a combined spatial and single-cell transcriptomic approach to define the cellular components of the stem cell niche, identify cell‒cell communication, and ultimately gain a comprehensive understanding of local and global SSPC regulatory networks within calcified tissue.</p>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2023-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10625929/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"71489486","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}
引用次数: 0
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