Perivascular Fibro-Adipogenic Progenitor Tracing during Post-Traumatic Osteoarthritis
| Autor: | Takashi Sono, Jiajia Xu, Amanda K. Huber, Benjamin Levi, Simone Marini, Masnsen Cherief, Sarah Miller, Ching Yun Hsu, Bruno Péault, Aaron W. James, Yiyun Wang |
|---|---|
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Pathology medicine.medical_specialty Knee Joint Mice Transgenic PDGFRA Fat pad Mural cell Article Pathology and Forensic Medicine Green fluorescent protein 03 medical and health sciences Mice 0302 clinical medicine Fibrosis Gene expression Osteoarthritis medicine Adipocytes Animals Cell Lineage Progenitor cell Infrapatellar fat pad business.industry Stem Cells Fibroblasts medicine.disease 030104 developmental biology Adipose Tissue business 030217 neurology & neurosurgery |
| Zdroj: | Am J Pathol |
| ISSN: | 1525-2191 |
| Popis: | 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-CreER(T2) 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. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|