iScience (May 2021)

Enhancing the chondrogenic potential of chondrogenic progenitor cells by deleting RAB5C

  • Jerome Nicolas Janssen,
  • Valerio Izzi,
  • Elvira Henze,
  • Gökhan Cingöz,
  • Florian Lowen,
  • David Küttner,
  • Ruth Neumann,
  • Christof Lenz,
  • Vicki Rosen,
  • Nicolai Miosge

Journal volume & issue
Vol. 24, no. 5
p. 102464

Abstract

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Summary: Osteoarthritis (OA) is the most prevalent chronic joint disease that affects a large proportion of the elderly population. Chondrogenic progenitor cells (CPCs) reside in late-stage OA cartilage tissue, producing a fibrocartilaginous extracellular matrix; these cells can be manipulated in vitro to deposit proteins of healthy articular cartilage.CPCs are under the control of SOX9 and RUNX2. In our earlier studies, we showed that a knockdown of RUNX2 enhanced the chondrogenic potential of CPCs. Here we demonstrate that CPCs carrying a knockout of RAB5C, a protein involved in endosomal trafficking, exhibited elevated expression of multiple chondrogenic markers, including the SOX trio, and increased COL2 deposition, whereas no changes in COL1 deposition were observed.We report RAB5C as an attractive target for future therapeutic approaches designed to increase the COL2 content in the diseased joint.

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