Bone Research最新文献_第8页

Interoceptive regulation of skeletal tissue homeostasis and repair. 骨骼组织稳态和修复的感受性调节。

IF 12.7 1区医学

Bone Research Pub Date : 2023-09-05 DOI: 10.1038/s41413-023-00285-6

Yao Xiao, Changhao Han, Yunhao Wang, Xinshu Zhang, Rong Bao, Yuange Li, Huajiang Chen, Bo Hu, Shen Liu

{"title":"Interoceptive regulation of skeletal tissue homeostasis and repair.","authors":"Yao Xiao, Changhao Han, Yunhao Wang, Xinshu Zhang, Rong Bao, Yuange Li, Huajiang Chen, Bo Hu, Shen Liu","doi":"10.1038/s41413-023-00285-6","DOIUrl":"10.1038/s41413-023-00285-6","url":null,"abstract":"Recent studies have determined that the nervous system can sense and respond to signals from skeletal tissue, a process known as skeletal interoception, which is crucial for maintaining bone homeostasis. The hypothalamus, located in the central nervous system (CNS), plays a key role in processing interoceptive signals and regulating bone homeostasis through the autonomic nervous system, neuropeptide release, and neuroendocrine mechanisms. These mechanisms control the differentiation of mesenchymal stem cells into osteoblasts (OBs), the activation of osteoclasts (OCs), and the functional activities of bone cells. Sensory nerves extensively innervate skeletal tissues, facilitating the transmission of interoceptive signals to the CNS. This review provides a comprehensive overview of current research on the generation and coordination of skeletal interoceptive signals by the CNS to maintain bone homeostasis and their potential role in pathological conditions. The findings expand our understanding of intersystem communication in bone biology and may have implications for developing novel therapeutic strategies for bone diseases.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2023-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10480189/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10180793","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

Inhibiting WNT secretion reduces high bone mass caused by Sost loss-of-function or gain-of-function mutations in Lrp5. 抑制WNT分泌可减少由Lrp5的Sost功能丧失或功能获得突变引起的高骨量。

IF 12.7 1区医学

Bone Research Pub Date : 2023-08-24 DOI: 10.1038/s41413-023-00278-5

Cassandra R Diegel, Ina Kramer, Charles Moes, Gabrielle E Foxa, Mitchell J McDonald, Zachary B Madaj, Sabine Guth, Jun Liu, Jennifer L Harris, Michaela Kneissel, Bart O Williams

{"title":"Inhibiting WNT secretion reduces high bone mass caused by Sost loss-of-function or gain-of-function mutations in Lrp5.","authors":"Cassandra R Diegel, Ina Kramer, Charles Moes, Gabrielle E Foxa, Mitchell J McDonald, Zachary B Madaj, Sabine Guth, Jun Liu, Jennifer L Harris, Michaela Kneissel, Bart O Williams","doi":"10.1038/s41413-023-00278-5","DOIUrl":"10.1038/s41413-023-00278-5","url":null,"abstract":"Proper regulation of Wnt signaling is critical for normal bone development and homeostasis. Mutations in several Wnt signaling components, which increase the activity of the pathway in the skeleton, cause high bone mass in human subjects and mouse models. Increased bone mass is often accompanied by severe headaches from increased intracranial pressure, which can lead to fatality and loss of vision or hearing due to the entrapment of cranial nerves. In addition, progressive forehead bossing and mandibular overgrowth occur in almost all subjects. Treatments that would provide symptomatic relief in these subjects are limited. Porcupine-mediated palmitoylation is necessary for Wnt secretion and binding to the frizzled receptor. Chemical inhibition of porcupine is a highly selective method of Wnt signaling inhibition. We treated three different mouse models of high bone mass caused by aberrant Wnt signaling, including homozygosity for loss-of-function in Sost, which models sclerosteosis, and two strains of mice carrying different point mutations in Lrp5 (equivalent to human G171V and A214V), at 3 months of age with porcupine inhibitors for 5-6 weeks. Treatment significantly reduced both trabecular and cortical bone mass in all three models. This demonstrates that porcupine inhibition is potentially therapeutic for symptomatic relief in subjects who suffer from these disorders and further establishes that the continued production of Wnts is necessary for sustaining high bone mass in these models.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10447437/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10447672","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

α-parvin controls chondrocyte column formation and regulates long bone development. α-细小蛋白控制软骨细胞柱的形成并调节长骨的发育。

IF 12.7 1区医学

Bone Research Pub Date : 2023-08-22 DOI: 10.1038/s41413-023-00284-7

Jifan Yuan, Ling Guo, Jiaxin Wang, Zhongjun Zhou, Chuanyue Wu

{"title":"α-parvin controls chondrocyte column formation and regulates long bone development.","authors":"Jifan Yuan, Ling Guo, Jiaxin Wang, Zhongjun Zhou, Chuanyue Wu","doi":"10.1038/s41413-023-00284-7","DOIUrl":"10.1038/s41413-023-00284-7","url":null,"abstract":"Endochondral ossification requires proper control of chondrocyte proliferation, differentiation, survival, and organization. Here we show that knockout of α-parvin, an integrin-associated focal adhesion protein, from murine limbs causes defects in endochondral ossification and dwarfism. The mutant long bones were shorter but wider, and the growth plates became disorganized, especially in the proliferative zone. With two-photon time-lapse imaging of bone explant culture, we provide direct evidence showing that α-parvin regulates chondrocyte rotation, a process essential for chondrocytes to form columnar structure. Furthermore, loss of α-parvin increased binucleation, elevated cell death, and caused dilation of the resting zones of mature growth plates. Single-cell RNA-seq analyses revealed alterations of transcriptome in all three zones (i.e., resting, proliferative, and hypertrophic zones) of the growth plates. Our results demonstrate a crucial role of α-parvin in long bone development and shed light on the cellular mechanism through which α-parvin regulates the longitudinal growth of long bones.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2023-08-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10444880/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10458153","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: 1

Metformin accelerates bone fracture healing by promoting type H vessel formation through inhibition of YAP1/TAZ expression. 二甲双胍通过抑制YAP1/TAZ表达促进H型血管形成，从而加速骨折愈合。

IF 12.7 1区医学

Bone Research Pub Date : 2023-08-16 DOI: 10.1038/s41413-023-00279-4

Zhe Ruan, Hao Yin, Teng-Fei Wan, Zhi-Rou Lin, Shu-Shan Zhao, Hai-Tao Long, Cheng Long, Zhao-Hui Li, Yu-Qi Liu, Hao Luo, Liang Cheng, Can Chen, Min Zeng, Zhang-Yuan Lin, Rui-Bo Zhao, Chun-Yuan Chen, Zhen-Xing Wang, Zheng-Zhao Liu, Jia Cao, Yi-Yi Wang, Ling Jin, Yi-Wei Liu, Guo-Qiang Zhu, Jing-Tao Zou, Jiang-Shan Gong, Yi Luo, Yin Hu, Yong Zhu, Hui Xie

{"title":"Metformin accelerates bone fracture healing by promoting type H vessel formation through inhibition of YAP1/TAZ expression.","authors":"Zhe Ruan, Hao Yin, Teng-Fei Wan, Zhi-Rou Lin, Shu-Shan Zhao, Hai-Tao Long, Cheng Long, Zhao-Hui Li, Yu-Qi Liu, Hao Luo, Liang Cheng, Can Chen, Min Zeng, Zhang-Yuan Lin, Rui-Bo Zhao, Chun-Yuan Chen, Zhen-Xing Wang, Zheng-Zhao Liu, Jia Cao, Yi-Yi Wang, Ling Jin, Yi-Wei Liu, Guo-Qiang Zhu, Jing-Tao Zou, Jiang-Shan Gong, Yi Luo, Yin Hu, Yong Zhu, Hui Xie","doi":"10.1038/s41413-023-00279-4","DOIUrl":"10.1038/s41413-023-00279-4","url":null,"abstract":"Due to increasing morbidity worldwide, fractures are becoming an emerging public health concern. This study aimed to investigate the effect of metformin on the healing of osteoporotic as well as normal fractures. Type H vessels have recently been identified as a bone-specific vascular subtype that supports osteogenesis. Here, we show that metformin accelerated fracture healing in both osteoporotic and normal mice. Moreover, metformin promoted angiogenesis in vitro under hypoxia as well as type H vessel formation throughout fracture healing. Mechanistically, metformin increased the expression of HIF-1α, an important positive regulator of type H vessel formation, by inhibiting the expression of YAP1/TAZ in calluses and hypoxia-cultured human microvascular endothelial cells (HMECs). The results of HIF-1α or YAP1/TAZ interference in hypoxia-cultured HMECs using siRNA further suggested that the enhancement of HIF-1α and its target genes by metformin is primarily through YAP1/TAZ inhibition. Finally, overexpression of YAP1/TAZ partially counteracted the effect of metformin in promoting type H vessel-induced angiogenesis-osteogenesis coupling during fracture repair. In summary, our findings suggest that metformin has the potential to be a therapeutic agent for fractures by promoting type H vessel formation through YAP1/TAZ inhibition.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2023-08-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10432554/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10016515","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

Phylobone: a comprehensive database of bone extracellular matrix proteins in human and model organisms. Phylobone:人类和模式生物骨细胞外基质蛋白的综合数据库。

IF 12.7 1区医学

Bone Research Pub Date : 2023-08-15 DOI: 10.1038/s41413-023-00281-w

Margalida Fontcuberta-Rigo, Miho Nakamura, Pere Puigbò

{"title":"Phylobone: a comprehensive database of bone extracellular matrix proteins in human and model organisms.","authors":"Margalida Fontcuberta-Rigo, Miho Nakamura, Pere Puigbò","doi":"10.1038/s41413-023-00281-w","DOIUrl":"10.1038/s41413-023-00281-w","url":null,"abstract":"The bone extracellular matrix (ECM) contains minerals deposited on highly crosslinked collagen fibrils and hundreds of non-collagenous proteins. Some of these proteins are key to the regulation of bone formation and regeneration via signaling pathways, and play important regulatory and structural roles. However, the complete list of bone extracellular matrix proteins, their roles, and the extent of individual and cross-species variations have not been fully captured in both humans and model organisms. Here, we introduce the most comprehensive resource of bone extracellular matrix (ECM) proteins that can be used in research fields such as bone regeneration, osteoporosis, and mechanobiology. The Phylobone database (available at https://phylobone.com ) includes 255 proteins potentially expressed in the bone extracellular matrix (ECM) of humans and 30 species of vertebrates. A bioinformatics pipeline was used to identify the evolutionary relationships of bone ECM proteins. The analysis facilitated the identification of potential model organisms to study the molecular mechanisms of bone regeneration. A network analysis showed high connectivity of bone ECM proteins. A total of 214 functional protein domains were identified, including collagen and the domains involved in bone formation and resorption. Information from public drug repositories was used to identify potential repurposing of existing drugs. The Phylobone database provides a platform to study bone regeneration and osteoporosis in light of (biological) evolution, and will substantially contribute to the identification of molecular mechanisms and drug targets.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2023-08-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10425349/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"10015037","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

Identification of an intronic enhancer regulating RANKL expression in osteocytic cells. 骨细胞中调控RANKL表达的内含子增强子的鉴定。

IF 12.7 1区医学

Bone Research Pub Date : 2023-08-11 DOI: 10.1038/s41413-023-00277-6

Minglu Yan, Masayuki Tsukasaki, Ryunosuke Muro, Yutaro Ando, Kazutaka Nakamura, Noriko Komatsu, Takeshi Nitta, Tadashi Okamura, Kazuo Okamoto, Hiroshi Takayanagi

{"title":"Identification of an intronic enhancer regulating RANKL expression in osteocytic cells.","authors":"Minglu Yan, Masayuki Tsukasaki, Ryunosuke Muro, Yutaro Ando, Kazutaka Nakamura, Noriko Komatsu, Takeshi Nitta, Tadashi Okamura, Kazuo Okamoto, Hiroshi Takayanagi","doi":"10.1038/s41413-023-00277-6","DOIUrl":"10.1038/s41413-023-00277-6","url":null,"abstract":"The bony skeleton is continuously renewed throughout adult life by the bone remodeling process, in which old or damaged bone is removed by osteoclasts via largely unknown mechanisms. Osteocytes regulate bone remodeling by producing the osteoclast differentiation factor RANKL (encoded by the TNFSF11 gene). However, the precise mechanisms underlying RANKL expression in osteocytes are still elusive. Here, we explored the epigenomic landscape of osteocytic cells and identified a hitherto-undescribed osteocytic cell-specific intronic enhancer in the TNFSF11 gene locus. Bioinformatics analyses showed that transcription factors involved in cell death and senescence act on this intronic enhancer region. Single-cell transcriptomic data analysis demonstrated that cell death signaling increased RANKL expression in osteocytic cells. Genetic deletion of the intronic enhancer led to a high-bone-mass phenotype with decreased levels of RANKL in osteocytic cells and osteoclastogenesis in the adult stage, while RANKL expression was not affected in osteoblasts or lymphocytes. These data suggest that osteocytes may utilize a specialized regulatory element to facilitate osteoclast formation at the bone surface to be resorbed by linking signals from cellular senescence/death and RANKL expression.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2023-08-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10415388/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9989028","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

Low back pain and osteoarthritis pain: a perspective of estrogen. 腰痛和骨关节炎疼痛:雌激素的视角。

IF 12.7 1区医学

Bone Research Pub Date : 2023-08-04 DOI: 10.1038/s41413-023-00280-x

Huiwen Pang, Shihui Chen, David M Klyne, David Harrich, Wenyuan Ding, Sidong Yang, Felicity Y Han

{"title":"Low back pain and osteoarthritis pain: a perspective of estrogen.","authors":"Huiwen Pang, Shihui Chen, David M Klyne, David Harrich, Wenyuan Ding, Sidong Yang, Felicity Y Han","doi":"10.1038/s41413-023-00280-x","DOIUrl":"10.1038/s41413-023-00280-x","url":null,"abstract":"Low back pain (LBP) is the world's leading cause of disability and is increasing in prevalence more rapidly than any other pain condition. Intervertebral disc (IVD) degeneration and facet joint osteoarthritis (FJOA) are two common causes of LBP, and both occur more frequently in elderly women than in other populations. Moreover, osteoarthritis (OA) and OA pain, regardless of the joint, are experienced by up to twice as many women as men, and this difference is amplified during menopause. Changes in estrogen may be an important contributor to these pain states. Receptors for estrogen have been found within IVD tissue and nearby joints, highlighting the potential roles of estrogen within and surrounding the IVDs and joints. In addition, estrogen supplementation has been shown to be effective at ameliorating IVD degeneration and OA progression, indicating its potential use as a therapeutic agent for people with LBP and OA pain. This review comprehensively examines the relationship between estrogen and these pain conditions by summarizing recent preclinical and clinical findings. The potential molecular mechanisms by which estrogen may relieve LBP associated with IVD degeneration and FJOA and OA pain are discussed.","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":null,"pages":null},"PeriodicalIF":12.7,"publicationDate":"2023-08-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10403578/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"9937363","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

Correction: FABP4 secreted by M1-polarized macrophages promotes synovitis and angiogenesis to exacerbate rheumatoid arthritis. 更正:m1极化巨噬细胞分泌FABP4促进滑膜炎和血管生成，加重类风湿关节炎。

IF 12.7 1区医学

Bone Research Pub Date : 2023-07-25 DOI: 10.1038/s41413-023-00271-y

Dong Guo, Chuangxin Lin, Yuheng Lu, Hong Guan, Weizhong Qi, Hongbo Zhang, Yan Shao, Chun Zeng, Rongkai Zhang, Haiyan Zhang, Xiaochun Bai, Daozhang Cai

引用次数: 0

Small-molecule amines: a big role in the regulation of bone homeostasis. 小分子胺:在调节骨稳态中起重要作用。

IF 12.7 1区医学

Bone Research Pub Date : 2023-07-24 DOI: 10.1038/s41413-023-00262-z

Qian Zhang, Jirong Yang, Nan Hu, Juan Liu, Huan Yu, Haobo Pan, Di Chen, Changshun Ruan

{"title":"Small-molecule amines: a big role in the regulation of bone homeostasis.","authors":"Qian Zhang, Jirong Yang, Nan Hu, Juan Liu, Huan Yu, Haobo Pan, Di Chen, Changshun Ruan","doi":"10.1038/s41413-023-00262-z","DOIUrl":"https://doi.org/10.1038/s41413-023-00262-z","url":null,"abstract":"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.","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}

引用次数: 0

Tppp3⁺ synovial/tendon sheath progenitor cells contribute to heterotopic bone after trauma. Tppp3+滑膜/腱鞘祖细胞有助于创伤后异位骨的形成。

IF 14.3 1区医学

Bone Research Pub Date : 2023-07-21 DOI: 10.1038/s41413-023-00272-x

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

{"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":"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.","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}

引用次数: 0