Cartilage Metabolism is Modulated by Synovial Fluid Through Metalloproteinase Activity

  • Eric Y. Sun
  • Allison K. M. Fleck
  • Ahmad E. Abu-Hakmeh
  • Alexandra Kotsakis
  • Garrett R. Leonard
  • Leo Q. Wan
Article
  • 88 Downloads

Abstract

Synovial fluid (SF) contains various cytokines that regulate chondrocyte metabolism and is dynamically associated with joint disease. The objective of this study was to investigate the effects of diluted normal SF on catabolic metabolism of articular cartilage under inflammatory conditions. For this purpose, SF was isolated from healthy bovine joints, diluted, and added to cartilage explant cultures stimulated with interleukin-1 (IL-1) for 12 days. The kinetic release of sulfated glycosaminoglycan (sGAG) and collagen, as well as nitric oxide and gelatinase matrix metalloproteinases were analyzed in the supernatant. Chondrocyte survival and matrix integrity in the explants were evaluated with Live/Dead and histological staining. Diluted synovial fluid treatment suppressed sGAG and collagen release, downregulated the production of nitric oxide and matrix metalloproteinases, reduced IL-1-induced chondrocyte death, and rescued matrix depletion. Our results demonstrate that normal SF can counteract inflammation-driven cartilage catabolism. This study reports on the protective function of healthy SF and the therapeutic potential of recapitulation of SF for cartilage repair.

Keywords

Articular cartilage Interleukin-1 (IL-1) Inflammation Matrix degradation Osteoarthritis 

Abbreviations

OA

Osteoarthritis

RA

Rheumatoid arthritis

ECM

Extracellular matrix

NO

Nitric oxide

MMP

Matrix metalloproteinase

SF

Synovial fluid

HA

Hyaluronic acid

sGAG

Sulfated glycosaminoglycan

Notes

Acknowledgments

Leo Q. Wan is a Pew Scholar in Biomedical Science, supported by Pew Charitable Trusts.

Conflict of interest

The authors declare no conflicts of interest.

Supplementary material

10439_2018_2010_MOESM1_ESM.pdf (2.3 mb)
Supplementary material 1 (PDF 2360 kb)

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Copyright information

© Biomedical Engineering Society 2018

Authors and Affiliations

  1. 1.Laboratory for Tissue Engineering and Morphogenesis, Department of Biomedical EngineeringRensselaer Polytechnic InstituteTroyUSA
  2. 2.Center for Biotechnology & Interdisciplinary StudiesRensselaer Polytechnic InstituteTroyUSA
  3. 3.Center for Modeling, Simulation and Imaging in MedicineRensselaer Polytechnic InstituteTroyUSA
  4. 4.Division of Orthopaedic SurgeryAlbany Medical CenterAlbanyUSA
  5. 5.Laboratory for Tissue Engineering and MorphogenesisRensselaer Polytechnic InstituteTroyUSA

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