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Deprecated: Implicit conversion from float 229.6 to int loses precision in C:\Inetpub\vhosts\kidney.de\httpdocs\pget.php on line 534 PLoS+One 2015 ; 10 (9): ä Nephropedia Template TP
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AFAP1 Is a Novel Downstream Mediator of TGF-?1 for CCN2 Induction in Osteoblasts #MMPMID26340021
Cho Y; Silverstein R; Geisinger MT; Martinkovich S; Corkill H; Cunnick JM; Planey SL; Arnott JA
PLoS One 2015[]; 10 (9): ä PMID26340021show ga
Background: CCN2 acts as an anabolic growth factor to regulate osteoblast differentiation and function. CCN2 is induced by TGF-?1 and acts as a mediator of TGF-?1 induced matrix production in osteoblasts and Src is required for CCN2 induction by TGF-?1; however, the molecular mechanisms that control CCN2 induction in osteoblasts are poorly understood. AFAP1 binds activated forms of Src and can direct the activation of Src in certain cell types, however a role for AFAP1 downstream of TGF-?1 or in osteoblats is undefined. In this study, we investigated the role of AFAP1 for CCN2 induction by TGF-?1 in primary osteoblasts. Results: We demonstrated that AFAP1 expression in osteoblasts occurs in a biphasic pattern with maximal expression levels occurring during osteoblast proliferation (~day 3), reduced expression during matrix production/maturation (~day 14?21), an a further increase in expression during mineralization (~day 21). AFAP1 expression is induced by TGF-?1 treatment in osteoblasts during days 7, 14 and 21. In osteoblasts, AFAP1 binds to Src and is required for Src activation by TGF-?1 and CCN2 promoter activity and protein induction by TGF-?1 treatment was impaired using AFAP1 siRNA, indicating the requirement of AFAP1 for CCN2 induction by TGF-?1. We also demonstrated that TGF-?1 induction of extracellular matrix protein collagen XIIa occurs in an AFAP1 dependent fashion. Conclusions: This study demonstrates that AFAP1 is an essential downstream signaling component of TGF-?1 for Src activation, CCN2 induction and collagen XIIa in osteoblasts.