Modulation of cartilage differentiation by melanoma inhibiting activity/cartilage-derived retinoic acid-sensitive protein (MIA/CD-RAP)
Experimental & Molecular Medicine
;
: 166-174, 2010.
Article
in English
| WPRIM
| ID: wpr-203596
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 alpha5 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.
Full text:
Available
Index:
WPRIM (Western Pacific)
Main subject:
Osteogenesis
/
Protein Binding
/
Signal Transduction
/
Cartilage
/
Cell Differentiation
/
Extracellular Matrix Proteins
/
Bone Morphogenetic Proteins
/
Chondrocytes
/
Integrin alpha5
/
Extracellular Signal-Regulated MAP Kinases
Type of study:
Diagnostic study
Limits:
Animals
/
Humans
Language:
English
Journal:
Experimental & Molecular Medicine
Year:
2010
Type:
Article
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