Identification of a new population of Tnn+ progenitors to form tendon enthesis fibrocartilage

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 cellu...

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Autori principali: Zhang, Tao (Autore) , Zhang, Lin (Autore) , Yuan, Ziyang (Autore) , Wang, Linfeng (Autore) , Hu, Jianzhong (Autore) , Skutella, Thomas (Autore) , Lu, Hongbin (Autore)
Natura: Article (Journal)
Lingua:inglese
Pubblicazione: 21 April 2026
In: Bone research
Year: 2026, Volume: 14, Fascicolo: 1, Pages: 1-14
ISSN:2095-6231
DOI:10.1038/s41413-026-00519-3
Accesso online:Verlag, kostenfrei, Volltext: https://doi.org/10.1038/s41413-026-00519-3
Verlag, kostenfrei, Volltext: https://www.nature.com/articles/s41413-026-00519-3
Testo
Note sull'autore:Tao Zhang, Lin Zhang, Ziyang Yuan, Linfeng Wang, Jianzhong Hu, Thomas Skutella and Hongbin Lu
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Riassunto: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.
Descrizione del documento:Im Titel ist das Pluszeichen bei Tnn+ hochgestellt
Gesehen am 03.06.2026
Descrizione fisica:Online Resource
ISSN:2095-6231
DOI:10.1038/s41413-026-00519-3