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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2010.1
- 수록면
- 166 - 174 (9page)
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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 α5 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.
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참고문헌 (23)
참고문헌 신청
Bauer R / 2006 / Regulation of integrin activity by MIA / J Biol Chem 281 : 11669 ~ 11677
Blesch A / 1994 / Cloning of a novel malignant melanoma-derived growth-regulatory protein, MIA / Cancer Res 54 : 5695 ~ 5701
Bobick BE / 2004 / The MEK-ERK signaling pathway is a negative regulator of cartilage-specific gene expression in embryonic limb mesenchyme / J Biol Chem 279 : 4588 ~ 4595
Bosserhoff AK / 1997 / Mouse CD-RAP/MIA gene: structure, chromosomal localization, and expression in cartilage and chondrosarcoma / Dev Dyn 208 : 516 ~ 525
Bosserhoff AK / 2003 / Active detachment involves inhibition of cell-matrix contacts of malignant melanoma cells by secretion of melanoma inhibitory activity / Lab Invest 83
Blesch A / 1994 / Cloning of a novel malignant melanoma-derived growth-regulatory protein, MIA / Cancer Res 54 : 5695 ~ 5701
Bobick BE / 2004 / The MEK-ERK signaling pathway is a negative regulator of cartilage-specific gene expression in embryonic limb mesenchyme / J Biol Chem 279 : 4588 ~ 4595
Bosserhoff AK / 1997 / Mouse CD-RAP/MIA gene: structure, chromosomal localization, and expression in cartilage and chondrosarcoma / Dev Dyn 208 : 516 ~ 525
Bosserhoff AK / 2003 / Active detachment involves inhibition of cell-matrix contacts of malignant melanoma cells by secretion of melanoma inhibitory activity / Lab Invest 83
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