Staebler, Sebastian and Lichtblau, Adrian and Gurbiel, Slavyana and Schubert, Thomas and Riechers, Alexander and Rottensteiner-Brandl, Ulrike and Bosserhoff, Anja (2023) MIA/CD-RAP Regulates MMP13 and Is a Potential New Disease-Modifying Target for Osteoarthritis Therapy. CELLS, 12 (2): 229. ISSN , 2073-4409
Full text not available from this repository. (Request a copy)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-1 beta-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.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MATRIX-METALLOPROTEINASE; GENE-EXPRESSION; CARTILAGE; PROTEIN; CLONING; DIFFERENTIATION; CHONDROCYTES; MODULATION; ACTIVATION; SYSTEM; osteoarthritis; MIA/CD-RAP; MMP13; therapeutic; signaling |
| Subjects: | 500 Science > 570 Life sciences 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 16 Mar 2024 15:39 |
| Last Modified: | 16 Mar 2024 15:40 |
| URI: | https://pred.uni-regensburg.de/id/eprint/60283 |
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