Intrinsic regeneration of osteoarthritic cartilage by unloading involves peri-articular stem cell activity: a joint effort

Concept

Spontaneous cartilage repair has recently been recognized as proof of concept in man. The collaborative group will delineate the unknown mechanisms by which mesenchymal stem cells (MSCs) in the context of the intraarticular milieu are involved in this repair activity.

Facts and figures

Project lead
Prof F Lafeber
UMC Utrecht
S.Mastbergen@UMCUtrecht.nl
FOREUM research grant: € 300.000
2015 - 2019

Meet the team

Prof F Lafeber
UMC Utrecht
Dr S Mastbergen
UMC Utrecht
Prof D McGonagle
University of Leeds
Prof F Berenbaum
Pierre and Marie Curie University, INSERM, AP-HP Saint-Antoine Hospital

Interim results

For the first time, we show that MSC number initially decline in synovial fluid (SF) upon KJD (figure 1A-B).

MSCs present in the SF showed changes in their gene expression profile upon KJD, most clearly observed during the treatment (3 weeks; figure 1C).

GDF5 and Grem1 presented with a statistically significant increased expression (p<0.05) during treatment while FAB4 expression was decreased. ACAN, PTH1R, and DDR expression had the tendency to increase over time. ADAMTS4, SOX9 and PTHLH expression showed a trend to decrease over time.

This explorative study provides for the first-time data on changes in SF MSC number and their gene expression profiles upon knee joint distraction. As such, first clues are provided for the involvement of MSCs in the regenerative process induced by joint distraction for end-stage knee OA.

The fall in SF MSCs number during distraction suggests adhesion to the arthritic surfaces in the KJD environment. Further studies are necessary to unravel the processes involved.

Publications

  • Intrinsic Cartilage Repair By Joint Distraction Is Triggered By a High Extracellular Matrix Turnover in Early Stages. Bedate AM, Mastbergen SC, Coeleveld K, et al. Osteoarthritis and Cartilage;24:S160-S161.
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  • Analysis of proteins in the synovial fluid during joint distraction: unravelling mechano-sensitive pathways that drive intrinsic cartilage repair? Fiona E Watt, Benjamin Hamid, Cesar Garriga, Andrew Judge, Renata Hrusecka, Roel Custers, Floris Lafeber, Simon Mastbergen, Tonia Vincent joint last author. Oral presentation at OARSI April 2018 (abstract 15). (OAC April 2018 Volume 26, Supplement 1, Pages S17–S18).
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  • Explaining the joint preservation as a result of joint distraction in clinical studies. Simon Mastbergen. Invited speaker at 5th Joint Preservation Congress at Warsaw, Poland September 2018.
  • Analysis of mechano-sensitive pathway markers in the synovial fluid during joint distraction. Fiona E Watt, Benjamin Hamid, Cesar Garriga, Andrew Judge, Renata Hrusecka, Roel Custers, Floris Lafeber, Simon Mastbergen, Tonia Vincent joint last author. Poster presentation at ICRS Focus Meeting December 2018, poster presentation at ORS February 2019
  • Longitudinal evaluation of synovial fluid and synovial fluid MSC transcript changes in subjects undergoing joint distraction. T. Baboolal, M.P. Jansen, E. Jones, T. Welting, P. Emans, F.P. Lafeber, D.G. McGonaggle, S.C. Mastbergen. Poster presentation at EULAR June 2019.

Abstracts EULAR 2019

FRI0518: Longitudinal evaluation of synovial fluid and synovial fluid MSC transcript changes in subjects undergoing joint distraction