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Publication : Platelet-derived growth factor receptor-? (PDGFR?) lineage tracing highlights perivascular cell to myofibroblast transdifferentiation during post-traumatic osteoarthritis.

First Author  Sono T Year  2020
Journal  J Orthop Res Volume  38
Issue  11 Pages  2484-2494
PubMed ID  32134140 Mgi Jnum  J:374455
Mgi Id  MGI:8259461 Doi  10.1002/jor.24648
Citation  Sono T, et al. (2020) Platelet-derived growth factor receptor-beta (PDGFRbeta) lineage tracing highlights perivascular cell to myofibroblast transdifferentiation during post-traumatic osteoarthritis. J Orthop Res 38(11):2484-2494
abstractText  Pericytes ubiquitously surround capillaries and microvessels within vascularized tissues and have diverse functions after tissue injury. In addition to regulation of angiogenesis and tissue regeneration after injury, pericytes also contribute to organ fibrosis. Destabilization of the medial meniscus (DMM) phenocopies post-traumatic osteoarthritis, yet little is known regarding the impact of DMM surgery on knee joint-associated pericytes and their cellular descendants. Here, inducible platelet-derived growth factor receptor-beta (PDGFRbeta)-CreER(T2) reporter mice were subjected to DMM surgery, and lineage tracing studies performed over an 8-week period. Results showed that at baseline PDGFRbeta reporter activity highlights abluminal perivascular cells within synovial and infrapatellar fat pad (IFP) tissues. DMM induces a temporospatially patterned increase in vascular density within synovial and subsynovial tissues. Marked vasculogenesis within IFP was accompanied by expansion of PDGFRbeta reporter(+) perivascular cell numbers, detachment of mGFP(+) descendants from vessel walls, and aberrant adoption of myofibroblastic markers among mGFP(+) cells including alpha-SMA, ED-A, and TGF-beta1. At later timepoints, fibrotic changes and vascular maturation occurred within subsynovial tissues, with the redistribution of PDGFRbeta(+) cellular descendants back to their perivascular niche. In sum, PDGFRbeta lineage tracing allows for tracing of perivascular cell fate within the diarthrodial joint. Further, destabilization of the joint induces vascular and fibrogenic changes of the IFP accompanied by perivascular to myofibroblast transdifferentiation.
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