Schubert, Thomas and Schlegel, Jacqueline and Schmid, Rainer and Opolka, Alfred and Graessel, Susanne and Humphries, Martin and Bosserhoff, Anja-Katrin (2010) Modulation of cartilage differentiation by melanoma inhibiting activity/cartilage-derived retinoic acid-sensitive protein (MIA/CD-RAP). EXPERIMENTAL AND MOLECULAR MEDICINE, 42 (3). pp. 166-174. ISSN 1226-3613, 2092-6413
Full text not available from this repository. (Request a copy)Abstract
Melanoma inhibiting activity/cartilage-derived retinoic acid-sensitive protein (MIA/CD-RAP) is a small soluble protein secreted from malignant melanoma cells and from chondrocytes. Recently, we revealed that MIA/CD-RAP can modulate bone morphogenetic protein (BMP)2-induced osteogenic differentiation into a chondrogenic direction. In the current study we aimed to find the molecular details of this MIA/CD-RAP function. Direct influence of MIA on BMP2 by protein-protein-interaction or modulating SMAD signaling was ruled out experimentally. Instead, we revealed inhibition of ERK signaling by MIA/CD-RAP. This inhibition is regulated via binding of MIA/CD-RAP to integrin alpha 5 and abolishing its activity. Active ERK signaling is known to block chondrogenic differentiation and we revealed induction of aggrecan expression in chondrocytes by treatment with MIA/CD-RAP or PD098059, an ERK inhibitor. In in vivo models we could support the role of MIA/CD-RAP in influencing osteogenic differentiation negatively. Further, MIA/CD-RAP-deficient mice revealed an enhanced calcified cartilage layer of the articular cartilage of the knee joint and disordered arrangement of chondrocytes. Taken together, our data indicate that MIA/CD-RAP stabilizes cartilage differentiation and inhibits differentiation into bone potentially by regulating signaling processes during differentiation.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | X COLLAGEN; CHONDROCYTE DIFFERENTIATION; ARTICULAR-CARTILAGE; GENE-EXPRESSION; MESSENGER-RNA; CELL; LOCALIZATION; INCREASE; PATHWAY; CLONING; bone morphogenetic protein 2; cartilage; cell differentiation; chondrocytes; MIA protein, human |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Orthopädie Medicine > Lehrstuhl für Pathologie |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 04 Aug 2020 12:18 |
| Last Modified: | 04 Aug 2020 12:18 |
| URI: | https://pred.uni-regensburg.de/id/eprint/24957 |
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