Perivascular Fibro-Adipogenic Progenitor Tracing during Post-Traumatic Osteoarthritis

Takashi Sono, Ching Yun Hsu, Yiyun Wang, Jiajia Xu, Masnsen Cherief, Simone Marini, Amanda K. Huber, Sarah Miller, Bruno Péault, Benjamin Levi, Aaron W. James*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


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 for use in visualizing perivascular cell contribution to fibrosis during arthritic changes have not been developed. Here, inducible Pdgfra-CreERT2 reporter mice were subjected to joint-destabilization surgery to induce arthritic changes, and cell lineage was traced over an 8-week period with a focus on the joint-associated fat pad. Results showed that, at baseline, inducible Pdgfra reporter activity highlighted adventitial and, to a lesser extent, pericytic cells within the infrapatellar fat pad. Joint-destabilization surgery was associated with marked fibrosis of the infrapatellar fat pad, accompanied by an expansion of perivascular Pdgfra-expressing cellular descendants, many of which adopted α-smooth muscle actin expression. Gene expression analysis of microdissected infrapatellar fat pad confirmed enrichment in membrane-bound green fluorescent protein/Pdgfra-expressing cells, along with a gene signature that corresponded with injury-associated fibro-adipogenic progenitors. Our results highlight dynamic changes in joint-associated perivascular fibro-adipogenic progenitors during osteoarthritis.

Original languageEnglish
Pages (from-to)1909-1920
Number of pages12
JournalAmerican Journal of Pathology
Issue number9
StatePublished - Sep 2020
Externally publishedYes


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