Identifying Signaling Pathways Driving Tendon Regeneration and Scar Formation

The TGFβ family of molecules is strongly implicated as the primary inducer of tendon and ligament formation in mammals. The TGFβ subfamily includes TGFβs, myostatin and activins, all of which activate the Smad2/3 pathway. Canonical signaling is initiated by ligand binding to type I and type II receptors, leading to Smad2/3 phosphorylation, nuclear translocation and transcription, while non-canonical signaling requires activation of mitogen-activated protein kinases (MAPK) following receptor binding.  Interestingly, TGFβ has been implicated both as a major regulator of tenogenesis and scar-mediated healing.  One major goal of the lab is identifying the downstream signals that distinguish tendon differentiation from fibrosis.  A complete understanding of TGFβ family signaling during tendon healing may enable therapies that attenuate fibrosis while enhancing tenogenesis. In addition to TGFβ, we have been employing transcriptional profiling by RNA-seq to identify and test other signaling pathways for tendon, such as Wnt signaling.