Article Text

Download PDFPDF
Hsp90β and p130cas: novel regulatory factors of MMP-13 expression in human osteoarthritic chondrocytes
  1. Z Fan1,
  2. G Tardif1,
  3. D Hum1,
  4. N Duval2,
  5. J-P Pelletier1,
  6. J Martel-Pelletier1
  1. 1
    Osteoarthritis Research Unit, University of Montreal Hospital Centre, Notre-Dame Hospital, Montreal, Quebec, Canada
  2. 2
    Pavillon des Charmilles, Vimont, Quebec, Canada
  1. Professor J Martel-Pelletier, Osteoarthritis Research Unit, University of Montreal Hospital Centre, Notre-Dame Hospital, Montreal, Quebec, Canada H2L 4M1; jm{at}


Background: Human osteoarthritic (OA) chondrocytes were previously classified into L (low)- and H (high)-OA according to matrix metalloproteinase-13 (MMP-13) basal levels and interleukin 1β (IL1β) inducibility. In H-OA chondrocytes, the regulatory proteins p130cas and nuclear matrix protein 4 (NMP4) acting on the MMP-13 promoter were identified.

Objective: To identify regulators of MMP-13 expression/production in human L-OA chondrocytes, to determine their effect on the expression of other MMPs and the effect of IL1β on these molecules.

Methods: The identification of the L-OA chondrocyte proteins interacting specifically with the AGRE site of the MMP-13 promoter was performed by mass spectrometry. Heat shock protein 90β (Hsp90β), p130cas and NMP4 small interfering RNAs (siRNAs) were transfected into L-OA chondrocytes and incubated with or without IL1β. Gene expression was determined by real-time PCR, MMP-1 and MMP-13 production by ELISA, and signalling pathway activation by western blotting and ELISA.

Results: Hsp90β was identified as a protein of the L-OA/AGRE-specific complex. Silencing p130cas and Hsp90β significantly increased MMP-13 expression (about four- and twofold, respectively) and production. sip130cas affected to a lesser extent MMP-1 expression (twofold) and production. siNMP4 showed no effect. Expression of MMP-2, -3, -9 and -14 was unaffected. Silencing both Hsp90β and p130cas had a significant additive effect on MMP-13, but not on MMP-1 expression, the level of which was similar to that with sip130cas alone. IL1β decreased p130cas and Hsp90β expression/production, indicating another pathway by which this cytokine upregulates MMP expression. The IL1β-triggered signalling pathways responsible for MMP upregulation were unaffected in the silenced cells.

Conclusion: This study illustrates the complex regulation of MMP-13 by showing the inhibitory effect of the two cytoplasmic molecules, p130cas and Hsp90β, in L-OA chondrocytes.

Statistics from


  • Competing interests: None.

  • Ethics approval: The Institutional Ethics Committee Board of the Notre-Dame Hospital approved the use of the human articular tissues.

Request Permissions

If you wish to reuse any or all of this article please use the link below which will take you to the Copyright Clearance Center’s RightsLink service. You will be able to get a quick price and instant permission to reuse the content in many different ways.