Identification of a new population of Tnn+progenitors to form tendon enthesis fibrocartilageOA
Elucidating the identity of enthesis-resident progenitors is critical for advancing regenerative strategies,particularly in the context of the long-standing question of how is fibrocartilage formed at tendon enthesis(bone-tendon interface)under mechanical loading.To address the question of cellular origins of entheseal fibrocartilage,we first employed spatial transcriptional and single cell sequencing to identify a novel population of Tnn⁺progenitor cells and delineate their lineage trajectories across developmental stages.Subsequently,we used a diphtheria toxin mediated ablation model targeting these Tnn⁺progenitors and demonstrated their functional importance,as ablation resulted in hypoplastic phenotypes characterized by impaired fibrocartilage maturation.Furthermore,comparative single-cell profiling between unloaded entheses and normal entheses revealed that tendon unloading significantly diminished both the abundance and chondrogenic potential of Tnn⁺progenitors.Collectively,these findings resolve fundamental questions regarding enthesis morphogenesis and provide mechanistic insights into how mechanical loading orchestrates this critical developmental process.
Tao Zhang;Lin Zhang;Ziyang Yuan;Linfeng Wang;Jianzhong Hu;Thomas Skutella;Hongbin Lu
Department of Sports Medicine,Xiangya Hospital,Central South University,Changsha,China Key Laboratory of Organ Injury,Aging and Regenerative Medicine of Hunan Province,Changsha,China National Clinical Research Center for Geriatric Diseases,Xiangya Hospital,Changsha,China Department of Neuroanatomy,Group for Regeneration and Reprogramming,Institute for Anatomy and Cell Biology,Medical Faculty,Heidelberg University,Heidelberg,GermanyDepartment of Sports Medicine,Xiangya Hospital,Central South University,Changsha,China Key Laboratory of Organ Injury,Aging and Regenerative Medicine of Hunan Province,Changsha,China National Clinical Research Center for Geriatric Diseases,Xiangya Hospital,Changsha,ChinaDepartment of Sports Medicine,Xiangya Hospital,Central South University,Changsha,China Key Laboratory of Organ Injury,Aging and Regenerative Medicine of Hunan Province,Changsha,China National Clinical Research Center for Geriatric Diseases,Xiangya Hospital,Changsha,ChinaDepartment of Sports Medicine,Xiangya Hospital,Central South University,Changsha,China Key Laboratory of Organ Injury,Aging and Regenerative Medicine of Hunan Province,Changsha,China National Clinical Research Center for Geriatric Diseases,Xiangya Hospital,Changsha,ChinaKey Laboratory of Organ Injury,Aging and Regenerative Medicine of Hunan Province,Changsha,China National Clinical Research Center for Geriatric Diseases,Xiangya Hospital,Changsha,China Department of Spine Surgery and Orthopaedics,Xiangya Hospital,Central South University,Changsha,ChinaDepartment of Neuroanatomy,Group for Regeneration and Reprogramming,Institute for Anatomy and Cell Biology,Medical Faculty,Heidelberg University,Heidelberg,GermanyDepartment of Sports Medicine,Xiangya Hospital,Central South University,Changsha,China Key Laboratory of Organ Injury,Aging and Regenerative Medicine of Hunan Province,Changsha,China National Clinical Research Center for Geriatric Diseases,Xiangya Hospital,Changsha,China
医药卫生
tnn progenitor cellscellular originsfibrocartilageprogenitor cellsentheseal fibrocartilageweadvancing regenerative strategiesparticularlysingle cell sequencingspatial transcriptional
《Bone Research》 2026 (3)
P.832-845,14
supported by the National Natural Science Foundation of China(NO.82230085,and 82272572).
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