Perivascular fibro-adipogenic progenitor tracing during post-traumatic osteoarthritis.

Abstract Perivascular mural cells surround capillaries and microvessels, and have diverse regenerative or fibrotic functions after tissue injury. Subsynovial fibrosis is a well known pathologic feature of osteoarthritis, yet transgenic animals to visualize perivascular cell contribution to fibrosis during arthritic changes have not been developed. Here, inducible Pdgfra-CreERT2 reporter mice were subjected to joint destabilization surgery in order to induce arthritic changes, and cell lineage traced over an 8 week period with a focus on the joint-associated fat pad. Results showed that at baseline inducible Pdgfra reporter activity highlights adventitial and to a lesser extent pericytic cells within the infrapatellar fat pad (IFP). Joint destabilization surgery induced marked fibrosis of the infrapatellar fat pad, accompanied by an expansion of perivascular Pdgfra-expressing cellular descendants, many of which adopted αSMA expression. Gene expression analysis of microdissected IFP confirmed enrichment in mGFP / Pdgfra-expressing cells, along with a gene signature which corresponded with injury associated fibro-adipogenic progenitors (FAPs). Our results highlight dynamic changes in joint-associated perivascular FAPs during osteoarthritis.