Increased levels of p21((CIP1/WAF1)) correlate with decreased chondrogenic differentiation potential in synovial membrane progenitor cells

Mech Ageing Dev. 2015 Jul:149:31-40. doi: 10.1016/j.mad.2015.05.005. Epub 2015 May 15.

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.

Keywords: Adult stem cells; Cell cycle; Chondrogenesis; Osteoarthritis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Cartilage, Articular / metabolism
  • Cell Cycle
  • Cell Differentiation*
  • Cell Survival
  • Chondrocytes / cytology
  • Cyclin-Dependent Kinase Inhibitor p21 / metabolism*
  • Female
  • Gene Expression Profiling
  • Humans
  • Inflammation / metabolism
  • Male
  • Mesenchymal Stem Cells / cytology
  • Middle Aged
  • Osteoarthritis / metabolism
  • RNA, Messenger / metabolism
  • Stem Cells / cytology*
  • Synovial Membrane / cytology*
  • Synovial Membrane / metabolism

Substances

  • CDKN1A protein, human
  • Cyclin-Dependent Kinase Inhibitor p21
  • RNA, Messenger