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bioRxiv · 10.1101/2022.03.03.482926

The role of TGFβ signaling in Gli1+ tendon and enthesis cells

Song, L.·Golman, M.·Abraham, A. C.·Zelzer, E.·Thomopoulos, S.
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Abstract

The development of musculoskeletal tissues such as tendon, enthesis, and bone relies on proliferation and differentiation of mesenchymal progenitor cells. Gli1+ cells have been described as putative stem cells in several tissues and are presumed to play critical roles in tissue formation and maintenance. For example, the enthesis, a fibrocartilage tissue that connects tendon to bone, is mineralized postnatally by a pool of Gli1+ progenitor cells. These cells are regulated by hedgehog signaling, but it is unclear if TGF{beta} signaling, necessary for tenogenesis, also plays a role in their behavior. To examine the role of TGF{beta} signaling in Gli1+ cell function, the receptor for TGF{beta}, TbR2, was deleted in Gli1-lineage cells in mice at P5. Decreased TGF{beta} signaling in these cells led to defects in enthesis formation by P56, including deficient bone morphometry underlying the enthesis and decreased mechanical properties. In vitro experiments using Gli1+ cells isolated from mouse tail tendons demonstrated that TGF{beta} controls cell proliferation and differentiation through canonical and non-canonical pathways and that TGF{beta} directly controls the tendon transcription factor scleraxis by binding to its distant enhancer. These results have implications in the development of treatments for tendon and enthesis pathologies.

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Song, L., Golman, M., Abraham, A. C., Zelzer, E., Thomopoulos, S.. 2022-03-04. The role of TGFβ signaling in Gli1+ tendon and enthesis cells. https://doi.org/10.1101/2022.03.03.482926

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