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

Cells MDPI

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.

Authors with CRIS profile

Sebastian Stäbler Lehrstuhl für Biochemie und Molekulare Medizin Adrian Lichtblau Lehrstuhl für Biochemie und Molekulare Medizin Slavyana Gurbiel Lehrstuhl für Biochemie und Molekulare Medizin Ulrike Rottensteiner-Brandl Lehrstuhl für Biochemie und Molekulare Medizin Anja Katrin Boßerhoff Lehrstuhl für Biochemie und Molekulare Medizin

Involved external institutions

Universitätsklinikum Regensburg DE Germany (DE)

How to cite

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://dx.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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