Partial Tendon Injury at the Tendon-to-Bone Enthesis Activates Skeletal Stem Cells (May, szac027, 2022)

The tendon enthesis plays a critical role in facilitating movement and reducing stress within joints. Partial enthesis injuries heal in a mechanically inferior manner and never achieve healthy tissue function. The cells responsible for tendon-to-bone healing remain incompletely characterized and their origin is unknown. Here, we evaluated the putative role of mouse skeletal stem cells (mSSCs) in the enthesis after partial-injury. We found that mSSCs were present at elevated levels within the enthesis following injury and that these cells downregulated TGF beta signaling pathway elements at both the RNA and protein levels. Exogenous application of TGF beta post-injury led to a reduced mSSC response and impaired healing, whereas treatment with a TGF beta inhibitor (SB43154) resulted in a more robust mSSC response. Collectively, these data suggest that mSSCs may augment tendon-to-bone healing by dampening the effects of TGF beta signaling within the mSSC niche.