Bone Research最新文献

{"title":"Multi-omics analysis of human tendon adhesion reveals that ACKR1-regulated macrophage migration is involved in regeneration","authors":"Xinshu Zhang, Yao Xiao, Bo Hu, Yanhao Li, Shaoyang Zhang, Jian Tian, Shuo Wang, Zaijin Tao, Xinqi Zeng, Ning-Ning Liu, Baojie Li, Shen Liu","doi":"10.1038/s41413-024-00324-w","DOIUrl":"https://doi.org/10.1038/s41413-024-00324-w","url":null,"abstract":"<p>Tendon adhesion is a common complication after tendon injury with the development of accumulated fibrotic tissues without effective anti-fibrotic therapies, resulting in severe disability. Macrophages are widely recognized as a fibrotic trigger during peritendinous adhesion formation. However, different clusters of macrophages have various functions and receive multiple regulation, which are both still unknown. In our current study, multi-omics analysis including single-cell RNA sequencing and proteomics was performed on both human and mouse tendon adhesion tissue at different stages after tendon injury. The transcriptomes of over 74 000 human single cells were profiled. As results, we found that SPP1⁺ macrophages, RGCC⁺ endothelial cells, ACKR1⁺ endothelial cells and ADAM12⁺ fibroblasts participated in tendon adhesion formation. Interestingly, despite specific fibrotic clusters in tendon adhesion, FOLR2⁺ macrophages were identified as an antifibrotic cluster by in vitro experiments using human cells. Furthermore, ACKR1 was verified to regulate FOLR2⁺ macrophages migration at the injured peritendinous site by transplantation of bone marrow from <i>Lysm-Cre;R26R</i>^{<i>tdTomato</i>} mice to lethally irradiated <i>Ackr1</i>^{<i>−/−</i>} mice (<i>Ackr1</i>^{<i>−/−</i>} chimeras; deficient in ACKR1) and control mice (WT chimeras). Compared with WT chimeras, the decline of FOLR2⁺ macrophages was also observed, indicating that ACKR1 was specifically involved in FOLR2⁺ macrophages migration. Taken together, our study not only characterized the fibrosis microenvironment landscape of tendon adhesion by multi-omics analysis, but also uncovered a novel antifibrotic cluster of macrophages and their origin. These results provide potential therapeutic targets against human tendon adhesion.</p>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"1 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2024-05-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140845417","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}

{"title":"Pannexins in the musculoskeletal system: new targets for development and disease progression","authors":"Yan Luo, Shengyuan Zheng, Wenfeng Xiao, Hang Zhang, Yusheng Li","doi":"10.1038/s41413-024-00334-8","DOIUrl":"https://doi.org/10.1038/s41413-024-00334-8","url":null,"abstract":"<p>During cell differentiation, growth, and development, cells can respond to extracellular stimuli through communication channels. Pannexin (Panx) family and connexin (Cx) family are two important types of channel-forming proteins. Panx family contains three members (Panx1-3) and is expressed widely in bone, cartilage and muscle. Although there is no sequence homology between Panx family and Cx family, they exhibit similar configurations and functions. Similar to Cxs, the key roles of Panxs in the maintenance of physiological functions of the musculoskeletal system and disease progression were gradually revealed later. Here, we seek to elucidate the structure of Panxs and their roles in regulating processes such as osteogenesis, chondrogenesis, and muscle growth. We also focus on the comparison between Cx and Panx. As a new key target, Panxs expression imbalance and dysfunction in muscle and the therapeutic potentials of Panxs in joint diseases are also discussed.</p>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"22 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2024-05-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140845122","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}

{"title":"Sorafenib inhibits ossification of the posterior longitudinal ligament by blocking LOXL2-mediated vascularization","authors":"Longqing Wang, Wenhao Jiang, Siyuan Zhao, Dong Xie, Qing Chen, Qi Zhao, Hao Wu, Jian Luo, Lili Yang","doi":"10.1038/s41413-024-00327-7","DOIUrl":"https://doi.org/10.1038/s41413-024-00327-7","url":null,"abstract":"<p>Ossification of the Posterior Longitudinal Ligament (OPLL) is a degenerative hyperostosis disease characterized by the transformation of the soft and elastic vertebral ligament into bone, resulting in limited spinal mobility and nerve compression. Employing both bulk and single-cell RNA sequencing, we elucidate the molecular characteristics, cellular components, and their evolution during the OPLL process at a single-cell resolution, and validate these findings in clinical samples. This study also uncovers the capability of ligament stem cells to exhibit endothelial cell-like phenotypes in vitro and in vivo. Notably, our study identifies LOXL2 as a key regulator in this process. Through gain-and loss-of-function studies, we elucidate the role of LOXL2 in the endothelial-like differentiation of ligament cells. It acts via the HIF1A pathway, promoting the secretion of downstream VEGFA and PDGF-BB. This function is not related to the enzymatic activity of LOXL2. Furthermore, we identify sorafenib, a broad-spectrum tyrosine kinase inhibitor, as an effective suppressor of LOXL2-mediated vascular morphogenesis. By disrupting the coupling between vascularization and osteogenesis, sorafenib demonstrates significant inhibition of OPLL progression in both BMP-induced and <i>enpp1</i> deficiency-induced animal models while having no discernible effect on normal bone mass. These findings underscore the potential of sorafenib as a therapeutic intervention for OPLL.</p>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"15 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2024-04-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140541800","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}

{"title":"Cell membrane vesicles derived from hBMSCs and hUVECs enhance bone regeneration","authors":"Dandan Wang, Yaru Guo, Boon Chin Heng, Xuehui Zhang, Yan Wei, Ying He, Mingming Xu, Bin Xia, Xuliang Deng","doi":"10.1038/s41413-024-00325-9","DOIUrl":"https://doi.org/10.1038/s41413-024-00325-9","url":null,"abstract":"<p>Bone tissue renewal can be enhanced through co-transplantation of bone mesenchymal stem cells (BMSCs) and vascular endothelial cells (ECs). However, there are apparent limitations in stem cell-based therapy which hinder its clinic translation. Hence, we investigated the potential of alternative stem cell substitutes for facilitating bone regeneration. In this study, we successfully prepared cell membrane vesicles (CMVs) from BMSCs and ECs. The results showed that BMSC-derived cell membrane vesicles (BMSC-CMVs) possessed membrane receptors involved in juxtacrine signaling and growth factors derived from their parental cells. EC-derived cell membrane vesicles (EC-CMVs) also contained BMP2 and VEGF derived from their parental cells. BMSC-CMVs enhanced tube formation and migration ability of hUVECs, while EC-CMVs promoted the osteogenic differentiation of hBMSCs in vitro. Using a rat skull defect model, we found that co-transplantation of BMSC-CMVs and EC-CMVs could stimulate angiogenesis and bone formation in vivo. Therefore, our research might provide an innovative and feasible approach for cell-free therapy in bone tissue regeneration.</p>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"2 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2024-04-09","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140538157","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}

{"title":"Skeletal interoception in osteoarthritis","authors":"Dinglong Yang, Jiawen Xu, Ke Xu, Peng Xu","doi":"10.1038/s41413-024-00328-6","DOIUrl":"https://doi.org/10.1038/s41413-024-00328-6","url":null,"abstract":"<p>The interoception maintains proper physiological conditions and metabolic homeostasis by releasing regulatory signals after perceving changes in the internal state of the organism. Among its various forms, skeletal interoception specifically regulates the metabolic homeostasis of bones. Osteoarthritis (OA) is a complex joint disorder involving cartilage, subchondral bone, and synovium. The subchondral bone undergoes continuous remodeling to adapt to dynamic joint loads. Recent findings highlight that skeletal interoception mediated by aberrant mechanical loads contributes to pathological remodeling of the subchondral bone, resulting in subchondral bone sclerosis in OA. The skeletal interoception is also a potential mechanism for chronic synovial inflammation in OA. In this review, we offer a general overview of interoception, specifically skeletal interoception, subchondral bone microenviroment and the aberrant subchondral remedeling. We also discuss the role of skeletal interoception in abnormal subchondral bone remodeling and synovial inflammation in OA, as well as the potential prospects and challenges in exploring novel OA therapies that target skeletal interoception.</p>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"36 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140333437","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}

{"title":"The pathogenic mechanism of syndactyly type V identified in a Hoxd13Q50R knock-in mice","authors":"Han Wang, Xiumin Chen, Xiaolu Meng, Yixuan Cao, Shirui Han, Keqiang Liu, Ximeng Zhao, Xiuli Zhao, Xue Zhang","doi":"10.1038/s41413-024-00322-y","DOIUrl":"https://doi.org/10.1038/s41413-024-00322-y","url":null,"abstract":"<p>Syndactyly type V (SDTY5) is an autosomal dominant extremity malformation characterized by fusion of the fourth and fifth metacarpals. In the previous publication, we first identified a heterozygous missense mutation Q50R in homeobox domain (HD) of <i>HOXD13</i> in a large Chinese family with SDTY5. In order to substantiate the pathogenicity of the variant and elucidate the underlying pathogenic mechanism causing limb malformation, transcription-activator-like effector nucleases (TALEN) was employed to generate a <i>Hoxd13</i>Q50R mutant mouse. The mutant mice exhibited obvious limb malformations including slight brachydactyly and partial syndactyly between digits 2–4 in the heterozygotes, and severe syndactyly, brachydactyly and polydactyly in homozygotes. Focusing on BMP2 and SHH/GREM1/AER-FGF epithelial mesenchymal (e-m) feedback, a crucial signal pathway for limb development, we found the ectopically expressed <i>Shh</i>, <i>Grem1</i> and <i>Fgf</i>8 and down-regulated <i>Bmp2</i> in the embryonic limb bud at E10.5 to E12.5. A transcriptome sequencing analysis was conducted on limb buds (LBs) at E11.5, revealing 31 genes that exhibited notable disparities in mRNA level between the <i>Hoxd13</i>Q50R homozygotes and the wild-type. These genes are known to be involved in various processes such as limb development, cell proliferation, migration, and apoptosis. Our findings indicate that the ectopic expression of <i>Shh</i> and <i>Fgf8</i>, in conjunction with the down-regulation of <i>Bmp2</i>, results in a failure of patterning along both the anterior-posterior and proximal-distal axes, as well as a decrease in interdigital programmed cell death (PCD). This cascade ultimately leads to the development of syndactyly and brachydactyly in heterozygous mice, and severe limb malformations in homozygous mice. These findings suggest that abnormal expression of <i>SHH, FGF8</i>, and <i>BMP2</i> induced by <i>HOXD13</i>Q50R may be responsible for the manifestation of human SDTY5.</p>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"46 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140333424","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}

{"title":"Piezo1 channel exaggerates ferroptosis of nucleus pulposus cells by mediating mechanical stress-induced iron influx","authors":"Ziqian Xiang, Pengfei Zhang, Chunwang Jia, Rongkun Xu, Dingren Cao, Zhaoning Xu, Tingting Lu, Jingwei Liu, Xiaoxiong Wang, Cheng Qiu, Wenyang Fu, Weiwei Li, Lei Cheng, Qiang Yang, Shiqing Feng, Lianlei Wang, Yunpeng Zhao, Xinyu Liu","doi":"10.1038/s41413-024-00317-9","DOIUrl":"https://doi.org/10.1038/s41413-024-00317-9","url":null,"abstract":"<p>To date, several molecules have been found to facilitate iron influx, while the types of iron influx channels remain to be elucidated. Here, Piezo1 channel was identified as a key iron transporter in response to mechanical stress. Piezo1-mediated iron overload disturbed iron metabolism and exaggerated ferroptosis in nucleus pulposus cells (NPCs). Importantly, Piezo1-induced iron influx was independent of the transferrin receptor (TFRC), a well-recognized iron gatekeeper. Furthermore, pharmacological inactivation of Piezo1 profoundly reduced iron accumulation, alleviated mitochondrial ROS, and suppressed ferroptotic alterations in stimulation of mechanical stress. Moreover, conditional knockout of Piezo1 (<i>Col2a1-CreERT Piezo1</i>^{<i>flox/flox</i>}) attenuated the mechanical injury-induced intervertebral disc degeneration (IVDD). Notably, the protective effect of Piezo1 deficiency in IVDD was dampened in <i>Piezo1/Gpx4</i> conditional double knockout (cDKO) mice (<i>Col2a1-CreERT Piezo1</i>^{<i>flox/flox</i>}<i>/Gpx4</i>^{<i>flox/flox</i>}). These findings suggest that Piezo1 is a potential determinant of iron influx, indicating that the Piezo1-iron-ferroptosis axis might shed light on the treatment of mechanical stress-induced diseases.</p>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"39 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2024-03-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140321871","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}

{"title":"Kdm6a-CNN1 axis orchestrates epigenetic control of trauma-induced spinal cord microvascular endothelial cell senescence to balance neuroinflammation for improved neurological repair","authors":"Chengjun Li, Tian Qin, Jinyun Zhao, Yuxin Jin, Yiming Qin, Rundong He, Tianding Wu, Chunyue Duan, Liyuan Jiang, Feifei Yuan, Hongbin Lu, Yong Cao, Jianzhong Hu","doi":"10.1038/s41413-024-00323-x","DOIUrl":"https://doi.org/10.1038/s41413-024-00323-x","url":null,"abstract":"<p>Cellular senescence assumes pivotal roles in various diseases through the secretion of proinflammatory factors. Despite extensive investigations into vascular senescence associated with aging and degenerative diseases, the molecular mechanisms governing microvascular endothelial cell senescence induced by traumatic stress, particularly its involvement in senescence-induced inflammation, remain insufficiently elucidated. In this study, we present a comprehensive demonstration and characterization of microvascular endothelial cell senescence induced by spinal cord injury (SCI). Lysine demethylase 6A (Kdm6a), commonly known as UTX, emerges as a crucial regulator of cell senescence in injured spinal cord microvascular endothelial cells (SCMECs). Upregulation of UTX induces senescence in SCMECs, leading to an amplified release of proinflammatory factors, specifically the senescence-associated secretory phenotype (SASP) components, thereby modulating the inflammatory microenvironment. Conversely, the deletion of UTX in endothelial cells shields SCMECs against senescence, mitigates the release of proinflammatory SASP factors, and promotes neurological functional recovery after SCI. UTX forms an epigenetic regulatory axis by binding to calponin 1 (CNN1), orchestrating trauma-induced SCMECs senescence and SASP secretion, thereby influencing neuroinflammation and neurological functional repair. Furthermore, local delivery of a senolytic drug reduces senescent SCMECs and suppresses proinflammatory SASP secretion, reinstating a local regenerative microenvironment and enhancing functional repair after SCI. In conclusion, targeting the UTX-CNN1 epigenetic axis to prevent trauma-induced SCMECs senescence holds the potential to inhibit SASP secretion, alleviate neuroinflammation, and provide a novel treatment strategy for SCI repair.</p>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"1 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2024-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140209679","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}

{"title":"β-Receptor blocker enhances the anabolic effect of PTH after osteoporotic fracture","authors":"Jie Huang, Tong Wu, Yi-Rong Jiang, Xuan-Qi Zheng, Huan Wang, Hao Liu, Hong Wang, Hui-Jie Leng, Dong-Wei Fan, Wan-Qiong Yuan, Chun-Li Song","doi":"10.1038/s41413-024-00321-z","DOIUrl":"https://doi.org/10.1038/s41413-024-00321-z","url":null,"abstract":"<p>The autonomic nervous system plays a crucial role in regulating bone metabolism, with sympathetic activation stimulating bone resorption and inhibiting bone formation. We found that fractures lead to increased sympathetic tone, enhanced osteoclast resorption, decreased osteoblast formation, and thus hastened systemic bone loss in ovariectomized (OVX) mice. However, the combined administration of parathyroid hormone (PTH) and the β-receptor blocker propranolol dramatically promoted systemic bone formation and osteoporotic fracture healing in OVX mice. The effect of this treatment is superior to that of treatment with PTH or propranolol alone. In vitro, the sympathetic neurotransmitter norepinephrine (NE) suppressed PTH-induced osteoblast differentiation and mineralization, which was rescued by propranolol. Moreover, NE decreased the PTH-induced expression of Runx2 but enhanced the expression of <i>Rankl</i> and the effect of PTH-stimulated osteoblasts on osteoclastic differentiation, whereas these effects were reversed by propranolol. Furthermore, PTH increased the expression of the circadian clock gene <i>Bmal1</i>, which was inhibited by NE-βAR signaling. <i>Bmal1</i> knockdown blocked the rescue effect of propranolol on the NE-induced decrease in PTH-stimulated osteoblast differentiation. Taken together, these results suggest that propranolol enhances the anabolic effect of PTH in preventing systemic bone loss following osteoporotic fracture by blocking the negative effects of sympathetic signaling on PTH anabolism.</p>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"24 1","pages":""},"PeriodicalIF":12.7,"publicationDate":"2024-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140182806","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}

{"title":"The HIF-1α/PLOD2 axis integrates extracellular matrix organization and cell metabolism leading to aberrant musculoskeletal repair.","authors":"Heeseog Kang, Amy L Strong, Yuxiao Sun, Lei Guo, Conan Juan, Alec C Bancroft, Ji Hae Choi, Chase A Pagani, Aysel A Fernandes, Michael Woodard, Juhoon Lee, Sowmya Ramesh, Aaron W James, David Hudson, Kevin N Dalby, Lin Xu, Robert J Tower, Benjamin Levi","doi":"10.1038/s41413-024-00320-0","DOIUrl":"10.1038/s41413-024-00320-0","url":null,"abstract":"<p><p>While hypoxic signaling has been shown to play a role in many cellular processes, its role in metabolism-linked extracellular matrix (ECM) organization and downstream processes of cell fate after musculoskeletal injury remains to be determined. Heterotopic ossification (HO) is a debilitating condition where abnormal bone formation occurs within extra-skeletal tissues. Hypoxia and hypoxia-inducible factor 1α (HIF-1α) activation have been shown to promote HO. However, the underlying molecular mechanisms by which the HIF-1α pathway in mesenchymal progenitor cells (MPCs) contributes to pathologic bone formation remain to be elucidated. Here, we used a proven mouse injury-induced HO model to investigate the role of HIF-1α on aberrant cell fate. Using single-cell RNA sequencing (scRNA-seq) and spatial transcriptomics analyses of the HO site, we found that collagen ECM organization is the most highly up-regulated biological process in MPCs. Zeugopod mesenchymal cell-specific deletion of Hif1α (Hoxa11-CreER^T2; Hif1a^fl/fl) significantly mitigated HO in vivo. ScRNA-seq analysis of these Hoxa11-CreER^T2; Hif1a^fl/fl mice identified the PLOD2/LOX pathway for collagen cross-linking as downstream of the HIF-1α regulation of HO. Importantly, our scRNA-seq data and mechanistic studies further uncovered that glucose metabolism in MPCs is most highly impacted by HIF-1α deletion. From a translational aspect, a pan-LOX inhibitor significantly decreased HO. A newly screened compound revealed that the inhibition of PLOD2 activity in MPCs significantly decreased osteogenic differentiation and glycolytic metabolism. This suggests that the HIF-1α/PLOD2/LOX axis linked to metabolism regulates HO-forming MPC fate. These results suggest that the HIF-1α/PLOD2/LOX pathway represents a promising strategy to mitigate HO formation.</p>","PeriodicalId":9134,"journal":{"name":"Bone Research","volume":"12 1","pages":"17"},"PeriodicalIF":12.7,"publicationDate":"2024-03-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10933265/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140109193","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}