Partial Tendon Injury at the Tendon-to-Bone Enthesis Activates Skeletal Stem Cells.
Ashley Lauren TitanMichael DavittDeshka FosterAnkit SalhotraSiddharth MenonKellen ChenEvan FahyMichael LopezR Ellen JonesIoana BaiuAustin BurchamMichael JanuszykGeoffrey GurtnerPaige FoxCharles ChanNatalina QuartoMichael LongakerPublished in: Stem cells translational medicine (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 TGFβ signaling pathway elements at both the RNA and protein levels. Exogenous application of TGFβ post-injury led to a reduced mSSC response and impaired healing, whereas treatment with a TGFβ 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 TGFβ signaling within the mSSC niche.
Keyphrases
- stem cells
- induced apoptosis
- anterior cruciate ligament reconstruction
- transforming growth factor
- rotator cuff
- signaling pathway
- bone mineral density
- cell cycle arrest
- epithelial mesenchymal transition
- soft tissue
- pi k akt
- bone loss
- endoplasmic reticulum stress
- oxidative stress
- bone regeneration
- cell death
- cell proliferation
- postmenopausal women
- stress induced
- body composition
- binding protein
- deep learning
- protein protein
- artificial intelligence