%0 Journal Article
%T Collagen XXIV (Col24¦Á1) Promotes Osteoblastic Differentiation and Mineralization through TGF-¦Â/Smads Signaling Pathway
%A Weizhuo Wang
%A Douglas Olson
%A Gang Liang
%A Renny T Franceschi
%A Chunyi Li
%A Bingyan Wang
%A Shuen Shiuan Wang
%A Shuying Yang
%J International Journal of Biological Sciences
%D 2012
%I Ivyspring International Publisher
%X Collagen XXIV (Col24¦Á1) is a recently discovered fibrillar collagen. It is known that mouse Col24¦Á1 is predominantly expressed in the forming skeleton of the mouse embryo, as well as in the trabecular bone and periosteum of the newborn mouse. However, the role and mechanism of Col24¦Á1 in osteoblast differentiation and mineralization remains unclear. By analyzing the expression pattern of Col24¦Á1, we confirmed that it is primarily expressed in bone tissues, and this expression gradually increased concomitant with the progression of osteoblast differentiation. Through the use of a lentivirus vector-mediated interference system, silencing Col24¦Á1 expression in MC3T3-E1 murine preosteoblastic cells resulted in significant inhibition of alkaline phosphatase (ALP) activity, cell mineralization, and the expression of osteoblast marker genes such as runt-related transcription factor 2 (Runx2), osteocalcin (OCN), ALP, and type I collagen (Col I). Subsequent overexpression not only rescued the deficiency in osteoblast differentiation from Col24¦Á1 silenced cells, but also enhanced osteoblastic differentiation in control cells. We further revealed that Col24¦Á1 interacts with integrin ¦Â3, and silencing Col24¦Á1 up-regulated the expression of Smad7 during osteoblast differentiation while at the same time inhibiting the phosphorylation of the Smad2/3 complex. These results suggest that Col24¦Á1 imparts some of its regulatory control on osteoblast differentiation and mineralization at least partially through interaction with integrin ¦Â3 and the transforming growth factor beta (TGF-¦Â) /Smads signaling pathway.
%U http://www.biolsci.org/v08p1310.htm