Osteoblast-derived CAR3 synergizing with collagen and bone sialoprotein enhances bone formationOA
Osteoblasts orchestrate the infiltration and crystallization of mineral precursors within collagen fibrils.Certain osteoblast-secreted mineralization-inducing proteins further stimulate bone formation.In this study,scRNA-seq analysis of murine skull and long bone revealed a striking expression pattern of carbonic anhydrase Ⅲ(Car3)in osteoblasts.We uncovered a pivotal role for CAR3 in osteoblast lineage cells,revealing its critical function in skeletal development and homeostasis.Conditional ablation of Car3 in Prx1-lineage cells resulted in osteopenia and markedly impaired osteoblast activity,underscoring its functional role.Mechanistically,the primary transcription factor RUNX2 directly regulated Car3 expression,mediating its spatiotemporal expression during development.Notably,CAR3 promoted collagen intrafibrillar mineralization by forming a ternary complex with COL1A1 and bone sialoprotein(BSP),thereby facilitating mineral deposition.Furthermore,CAR3-functionalized scaffolds significantly improved bone repair and regeneration by promoting both matrix mineralization and recruitment of Prx1-lineage cells.These findings establish CAR3 as a critical coordinator of osteoblast differentiation and collagen interfibrillar mineralization,positioning it as a central mediator for maintaining skeletal integrity and enabling regeneration.
Xiaoxin Ma;Qing He;Chen Ye;Jinglun Zhang;Xinyi Zhou;Yuxuan Zhang;Tian Gan;Zhe Li;Fangfang Song;Yufeng Zhang
State Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration,Key Laboratory of Oral Biomedicine Ministry of Education,Hubei Key Laboratory of Stomatology,School&Hospital of Stomatology,Wuhan University,Wuhan,China Hospital of Stomatology,Sun Yat-Sen University,Guangzhou,Guangdong,China Medical Research Institute,School of Medicine,Wuhan University,Wuhan,ChinaState Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration,Key Laboratory of Oral Biomedicine Ministry of Education,Hubei Key Laboratory of Stomatology,School&Hospital of Stomatology,Wuhan University,Wuhan,ChinaState Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration,Key Laboratory of Oral Biomedicine Ministry of Education,Hubei Key Laboratory of Stomatology,School&Hospital of Stomatology,Wuhan University,Wuhan,China Medical Research Institute,School of Medicine,Wuhan University,Wuhan,ChinaState Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration,Key Laboratory of Oral Biomedicine Ministry of Education,Hubei Key Laboratory of Stomatology,School&Hospital of Stomatology,Wuhan University,Wuhan,China Nanjing Stomatological Hospital,Affiliated Hospital of Medical School,Institute of Stomatology,Nanjing University,Nanjing,ChinaState Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration,Key Laboratory of Oral Biomedicine Ministry of Education,Hubei Key Laboratory of Stomatology,School&Hospital of Stomatology,Wuhan University,Wuhan,China Medical Research Institute,School of Medicine,Wuhan University,Wuhan,ChinaState Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration,Key Laboratory of Oral Biomedicine Ministry of Education,Hubei Key Laboratory of Stomatology,School&Hospital of Stomatology,Wuhan University,Wuhan,China Medical Research Institute,School of Medicine,Wuhan University,Wuhan,ChinaState Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration,Key Laboratory of Oral Biomedicine Ministry of Education,Hubei Key Laboratory of Stomatology,School&Hospital of Stomatology,Wuhan University,Wuhan,China Medical Research Institute,School of Medicine,Wuhan University,Wuhan,ChinaState Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration,Key Laboratory of Oral Biomedicine Ministry of Education,Hubei Key Laboratory of Stomatology,School&Hospital of Stomatology,Wuhan University,Wuhan,China Medical Research Institute,School of Medicine,Wuhan University,Wuhan,ChinaState Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration,Key Laboratory of Oral Biomedicine Ministry of Education,Hubei Key Laboratory of Stomatology,School&Hospital of Stomatology,Wuhan University,Wuhan,ChinaState Key Laboratory of Oral&Maxillofacial Reconstruction and Regeneration,Key Laboratory of Oral Biomedicine Ministry of Education,Hubei Key Laboratory of Stomatology,School&Hospital of Stomatology,Wuhan University,Wuhan,China Medical Research Institute,School of Medicine,Wuhan University,Wuhan,China
医药卫生
bone sialoproteinmineral precursorscarbonic anhydrasebone formationcollagen fibrilscertainosteoblastscollagenrunx
《International Journal of Oral Science》 2026 (3)
P.374-385,12
supported by the National Natural Science Foundation of China(82530028,82220108018 and 82401077)the Hubei Provincial Natural Science Foundation of China(2024AFB738)the Interdisciplinary Research Project of School of Stomatology Wuhan University(XNJC202302)the China Postdoctoral Science Foundation(2024M763824)the Natural Science Foundation of Jiangsu Province(BK20240266)。
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