MIA/CD-RAP Regulates MMP13 and Is a Potential New Disease-Modifying Target for Osteoarthritis Therapy

Stäbler S, Lichtblau A, Gurbiel S, Schubert T, Riechers A, Rottensteiner-Brandl U, Boßerhoff AK (2023)


Publication Type: Journal article

Publication year: 2023

Journal

Book Volume: 12

Article Number: 229

Journal Issue: 2

DOI: 10.3390/cells12020229

Abstract

Melanoma inhibitory activity/cartilage-derived retinoicacid-sensitive protein (MIA/CD-RAP) is a protein expressed and secreted by chondrocytes and cartilaginous tissues. MIA/CD-RAP-deficient mice develop milder osteoarthritis than wildtype mice. In this study, we investigated MIA/CD-RAP downstream targets to explain this reduced disease development. As a possible mediator, we could detect matrix metalloproteinase 13 (MMP13), and the influence of MIA/CD-RAP on MMP13 regulation was analyzed in vitro using SW1353 chondrosarcoma cells and primary chondrocytes. The femoral head cartilage of WT and MIA/CD-RAP −/− mice were cultured ex vivo to further investigate MMP13 activity. Finally, osteoarthritis was surgically induced via DMM in C57BL/6 mice, and the animals were treated with an MIA/CD-RAP inhibitory peptide by subcutaneously implanted pellets. MMP13 was regulated by MIA/CD-RAP in SW1353 cells, and MIA/CD-RAP −/− murine chondrocytes showed less expression of MMP13. Further, IL-1β-treated MIA/CD-RAP −/− chondrocytes displayed less MMP13 expression and activity. Additionally, MIA/CD-RAP-deficient ex vivo cultured cartilage explants showed less MMP13 activity as well as reduced cartilage degradation. The mice treated with the MIA/CD-RAP inhibitory peptide showed less osteoarthritis development. Our findings revealed MIA/CD-RAP as a new regulator of MMP13 and highlighted its role as a potential new target for osteoarthritis therapy.

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APA:

Stäbler, S., Lichtblau, A., Gurbiel, S., Schubert, T., Riechers, A., Rottensteiner-Brandl, U., & Boßerhoff, A.K. (2023). MIA/CD-RAP Regulates MMP13 and Is a Potential New Disease-Modifying Target for Osteoarthritis Therapy. Cells, 12(2). https://doi.org/10.3390/cells12020229

MLA:

Stäbler, Sebastian, et al. "MIA/CD-RAP Regulates MMP13 and Is a Potential New Disease-Modifying Target for Osteoarthritis Therapy." Cells 12.2 (2023).

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