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

Research output: Contribution to journalArticle

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 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 (US)
Pages (from-to)1909-1920
Number of pages12
JournalAmerican Journal of Pathology
Volume190
Issue number9
DOIs
StatePublished - Sep 2020

ASJC Scopus subject areas

  • Pathology and Forensic Medicine

Fingerprint Dive into the research topics of 'Perivascular Fibro-Adipogenic Progenitor Tracing during Post-Traumatic Osteoarthritis'. Together they form a unique fingerprint.

  • Cite this

    Sono, T., Hsu, C. Y., Wang, Y., Xu, J., Cherief, M., Marini, S., Huber, A. K., Miller, S., Péault, B., Levi, B., & James, A. W. (2020). Perivascular Fibro-Adipogenic Progenitor Tracing during Post-Traumatic Osteoarthritis. American Journal of Pathology, 190(9), 1909-1920. https://doi.org/10.1016/j.ajpath.2020.05.017