title: Increased levels of p21((CIP1/WAF1)) correlate with decreased chondrogenic differentiation potential in synovial membrane progenitor cells.
abstract: Cartilage injuries are a major concern in the field of orthopedics. They occur following trauma, as well as from a variety of pathological conditions including Osteoarthritis (OA). Although cartilage does not exhibit robust endogenous repair, it has been demonstrated that modulating the activity of p21 can increase the regenerative abilities of cartilage in vitro and in vivo. Since the synovial membrane is abundant with mesenchymal progenitor cells (MPCs) capable of differentiating into cartilage both in vitro and in vivo, we examined if p21 expression levels varied between MPCs derived from normal vs. OA knee joints. Analysis of p21 at the mRNA and protein levels within normal and OA MPCs demonstrated differential levels of expression between these two groups, with OA MPCs having higher p21 expression levels. The higher levels of p21 in OA MPCs are also correlated with a decreased chondrogenic differentiation capacity and synovial inflammation, however, there was no evidence of senescence in the OA cells. The results of this study suggest that cell cycle regulation in MPCs may be altered in OA and that modulation of this pathway may have therapeutic potential once the mechanism by which this regulates stem/progenitor cells is better understood.
authors.affiliation: University of Calgary, Biomedical Engineering, Calgary, Alberta, Canada; McCaig Institute, University of Calgary, Alberta, Canada. Electronic address: anand.masson@gmail.com.
authors.forename: Anand Oliveira
authors.initials: AO
authors.lastname: Masson
authors.affiliation: University of Calgary, Department of Surgery, Calgary, Alberta, Canada; McCaig Institute, University of Calgary, Alberta, Canada; Technische Universitat Dresden, Dresden, Germany. Electronic address: ricarda.hess@tu-dresden.de.
authors.forename: Ricarda
authors.initials: R
authors.lastname: Hess
authors.affiliation: McCaig Institute, University of Calgary, Alberta, Canada. Electronic address: icehouse.obrien@gmail.com.
authors.forename: Kate
authors.initials: K
authors.lastname: O'Brien
authors.affiliation: University of Calgary, Biomedical Engineering, Calgary, Alberta, Canada; McCaig Institute, University of Calgary, Alberta, Canada. Electronic address: karri.bertram@ucalgary.ca.
authors.forename: Karri L
authors.initials: KL
authors.lastname: Bertram
authors.affiliation: McCaig Institute, University of Calgary, Alberta, Canada. Electronic address: ptailor@ucalgary.ca.
authors.forename: Pankaj
authors.initials: P
authors.lastname: Tailor
authors.affiliation: McCaig Institute, University of Calgary, Alberta, Canada. Electronic address: irvinet@uvic.ca.
authors.forename: Edward
authors.initials: E
authors.lastname: Irvine
authors.affiliation: University of Calgary, Biomedical Engineering, Calgary, Alberta, Canada; McCaig Institute, University of Calgary, Alberta, Canada. Electronic address: guomin.ren@ucalgary.ca.
authors.forename: Guomin
authors.initials: G
authors.lastname: Ren
authors.affiliation: University of Calgary, Biomedical Engineering, Calgary, Alberta, Canada; University of Calgary, Department of Surgery, Calgary, Alberta, Canada; McCaig Institute, University of Calgary, Alberta, Canada. Electronic address: rkrawetz@ucalgary.ca.
authors.forename: Roman J
authors.initials: RJ
authors.lastname: Krawetz
mesh_terms: D000328:Adult; D000368:Aged; D002358:Cartilage, Articular / Q000378:metabolism; D002453:Cell Cycle; D002454:Cell Differentiation; D002470:Cell Survival; D019902:Chondrocytes / Q000166:cytology; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000378:metabolism*; D005260:Female; D020869:Gene Expression Profiling; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008297:Male; D059630:Mesenchymal Stem Cells / Q000166:cytology; D008875:Middle Aged; D010003:Osteoarthritis / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D013234:Stem Cells / Q000166:cytology*; D013583:Synovial Membrane / Q000166:cytology* / Q000378:metabolism
chemical_list: C493956:CDKN1A protein, human; D050759:Cyclin-Dependent Kinase Inhibitor p21; D012333:RNA, Messenger
keywords: Adult stem cells; Cell cycle; Chondrogenesis; Osteoarthritis