@article{2331cd3ed18847a2ae99fa5aa9af9825,
title = "Platelet-derived growth factor receptor-β (PDGFRβ) lineage tracing highlights perivascular cell to myofibroblast transdifferentiation during post-traumatic osteoarthritis",
abstract = "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-β (PDGFRβ)-CreERT2 reporter mice were subjected to DMM surgery, and lineage tracing studies performed over an 8-week period. Results showed that at baseline PDGFRβ 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 PDGFRβ reporter+ perivascular cell numbers, detachment of mGFP+ descendants from vessel walls, and aberrant adoption of myofibroblastic markers among mGFP+ cells including α-SMA, ED-A, and TGF-β1. At later timepoints, fibrotic changes and vascular maturation occurred within subsynovial tissues, with the redistribution of PDGFRβ+ cellular descendants back to their perivascular niche. In sum, PDGFRβ 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.",
keywords = "DMM, PDGFRβ, myofibroblast, pericyte, perivascular stem cell",
author = "Takashi Sono and Hsu, {Ching Yun} and Stefano Negri and Sarah Miller and Yiyun Wang and Jiajia Xu and Meyers, {Carolyn A.} and Bruno Peault and James, {Aaron W.}",
note = "Funding Information: AWJ was supported by the NIH/NIAMS (R01 AR070773 and K08 AR068316), NIH/NIDCR (R21 DE027922), USAMRAA through the Peer-Reviewed Medical Research Program (W81XWH-180109121 and W81XWH-18-1-0336), and Department of Defense through the Broad Agency Announcement (W81XWH-18-10613), American Cancer Society (Research Scholar Grant, RSG-18-027-01-CSM), the Maryland Stem Cell Research Foundation, and MTF Biologics. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Health, Department of Defense, or US Army. AWJ is a member of the scientific advisory board for Novadip Biosciences for work unrelated to the current project. Funding Information: AWJ was supported by the NIH/NIAMS (R01 AR070773 and K08 AR068316), NIH/NIDCR (R21 DE027922), USAMRAA through the Peer‐Reviewed Medical Research Program (W81XWH‐180109121 and W81XWH‐18‐1‐0336), and Department of Defense through the Broad Agency Announcement (W81XWH‐18‐10613), American Cancer Society (Research Scholar Grant, RSG‐18‐027‐01‐CSM), the Maryland Stem Cell Research Foundation, and MTF Biologics. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institute of Health, Department of Defense, or US Army. AWJ is a member of the scientific advisory board for Novadip Biosciences for work unrelated to the current project. Publisher Copyright: {\textcopyright} 2020 Orthopaedic Research Society. Published by Wiley Periodicals, Inc.",
year = "2020",
month = nov,
day = "1",
doi = "10.1002/jor.24648",
language = "English (US)",
volume = "38",
pages = "2484--2494",
journal = "Journal of Orthopaedic Research",
issn = "0736-0266",
publisher = "John Wiley and Sons Inc.",
number = "11",
}