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Cartilage Metabolism is Modulated by Synovial Fluid Through Metalloproteinase Activity

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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.

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Abbreviations

OA:

Osteoarthritis

RA:

Rheumatoid arthritis

ECM:

Extracellular matrix

NO:

Nitric oxide

MMP:

Matrix metalloproteinase

SF:

Synovial fluid

HA:

Hyaluronic acid

sGAG:

Sulfated glycosaminoglycan

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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.

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Author notes

  1. Eric Y. Sun and Allison K. M. Fleck have contributed equally to this study.

Authors and Affiliations

  1. Laboratory for Tissue Engineering and Morphogenesis, Department of Biomedical Engineering, Rensselaer Polytechnic Institute, 110 8th St, Troy, NY, 12180, USA

    Eric Y. Sun, Allison K. M. Fleck, Ahmad E. Abu-Hakmeh, Alexandra Kotsakis & Leo Q. Wan

  2. Center for Biotechnology & Interdisciplinary Studies, Rensselaer Polytechnic Institute, 110 8th St, Troy, NY, 12180, USA

    Eric Y. Sun & Leo Q. Wan

  3. Center for Modeling, Simulation and Imaging in Medicine, Rensselaer Polytechnic Institute, 110 8th St, Troy, NY, 12180, USA

    Leo Q. Wan

  4. Division of Orthopaedic Surgery, Albany Medical Center, 43 New Scotland Avenue, Albany, NY, 12208, USA

    Garrett R. Leonard

  5. Laboratory for Tissue Engineering and Morphogenesis, Rensselaer Polytechnic Institute, Biotech 2147, 110 8th Street, Troy, NY, 12180, USA

    Leo Q. Wan

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  1. Eric Y. Sun
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Correspondence to Leo Q. Wan.

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Associate Editor Michael S. Detamore oversaw the review of this article.

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Sun, E.Y., Fleck, A.K.M., Abu-Hakmeh, A.E. et al. Cartilage Metabolism is Modulated by Synovial Fluid Through Metalloproteinase Activity. Ann Biomed Eng 46, 810–818 (2018). https://doi.org/10.1007/s10439-018-2010-1

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