TY - JOUR
T1 - Perivascular Fibro-Adipogenic Progenitor Tracing during Post-Traumatic Osteoarthritis
AU - Sono, Takashi
AU - Hsu, Ching Yun
AU - Wang, Yiyun
AU - Xu, Jiajia
AU - Cherief, Masnsen
AU - Marini, Simone
AU - Huber, Amanda K.
AU - Miller, Sarah
AU - Péault, Bruno
AU - Levi, Benjamin
AU - James, Aaron W.
N1 - Funding Information:
Supported by the NIH/ National Institute of Arthritis and Musculoskeletal and Skin Diseases grants R01 AR070773 (A.W.J.) and K08 AR068316 (A.W.J.); NIH/ National Institute of Dental and Craniofacial Research grant R21 DE027922 (A.W.J.); US Army Medical Research Acquisition Activity (USAMRAA) grants W81XWH-180109121 (A.W.J.), W81XWH-18-1-0336 (A.W.J.), W81XWH-18-10613 (A.W.J.), and W81XWH-18-1-0653 (B.L.); American Cancer Society (ACS) Research Scholar grant RSG-18-027-01-CSM (A.W.J.); the Maryland Stem Cell Research Foundation (A.W.J.); MTF Biologics (A.W.J.); NIH grants R01GM123069 (B.L.) and R01AR071379 (B.L.); and the ACS Clowes Award (B.L.).
Publisher Copyright:
© 2020 American Society for Investigative Pathology
PY - 2020/9
Y1 - 2020/9
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ajpath.2020.05.017
DO - 10.1016/j.ajpath.2020.05.017
M3 - Article
C2 - 32533926
AN - SCOPUS:85089490221
SN - 0002-9440
VL - 190
SP - 1909
EP - 1920
JO - American Journal of Pathology
JF - American Journal of Pathology
IS - 9
ER -