Truncated Human LMP-1 Triggers Differentiation of C2C12 Cells to an Osteoblastic Phenotype in vitro
Authors: FEI, Qinming; BODEN, Scott D.; SANGADALA, Sreedhara; VIGGESWARAPU, Manjula; LIU, Yunshan; TITUS, Louisa
Source: Acta Biochimica et Biophysica Sinica, Volume 39, Number 9, September 2007 , pp. 693-700(8)
Publisher: Blackwell Publishing
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Abstract:
LIM mineralization protein-1 (LMP-1) is a novel intracellular osteoinductive protein that has been shown to induce bone formation both in vitro and in vivo. LMP-1 contains an N-terminal PDZ domain and three C-terminal LIM domains. In this study, we investigated whether a truncated form of human LMP-1 (hLMP-1[t]), lacking the three C-terminal LIM domains, triggers the differentiation of pluripotent myoblastic C2C12 cells to the osteoblast lineage. C2C12 cells were transiently transduced with Ad5-hLMP-1 (t)-green fluorescent protein or viral vector control. The expression of hLMP-1(t) RNA and the truncated protein were examined. The results showed that hLMP-1(t) blocked myotube formation in C2C12 cultures and significantly enhanced the alkaline phosphatase (ALP) activity. In addition, the expressions of ALP, osteocalcin, and bone morphogenetic protein (BMP)-2 and BMP-7 genes were also increased. The induction of these key osteogenic markers suggests that hLMP-1(t) can trigger the pluripotent myoblastic C2C12 cells to differentiate into osteoblastic lineage, thus extending our previous observation that LMP-1 and LMP-1(t) enhances the osteoblastic phenotype in cultures of cells already committed to the osteoblastic lineage. Therefore, C2C12 cells are an appropriate model system for the examination of LMP-1 induction of the osteoblastic phenotype and the study of mechanisms of LMP-1 action.Keywords: LIM mineralization protein-1; osteoblast; differentiation; C2C12
Document Type: Research article
DOI: 10.1111/j.1745-7270.2007.00333.x
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