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Insulin‐like growth factor‐1 promotes osteogenic differentiation and collagen I alpha 2 synthesis via induction of mRNA ‐binding protein LARP 6 expression
Author(s) -
Guo Yue,
Tang ChenYi,
Man XiaoFei,
Tang HaoNeng,
Tang Jun,
Zhou CiLa,
Tan ShuWen,
Wang Min,
Feng YunZhi,
Zhou HouDe
Publication year - 2017
Publication title -
development, growth and differentiation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.864
H-Index - 66
eISSN - 1440-169X
pISSN - 0012-1592
DOI - 10.1111/dgd.12342
Subject(s) - microbiology and biotechnology , messenger rna , chemistry , alpha (finance) , growth factor , biology , biochemistry , gene , receptor , medicine , construct validity , nursing , patient satisfaction
This study explored the mechanism underlying the stimulation of collagen synthesis and osteoblastic differentiation by insulin‐like growth factor 1 ( IGF 1) in primary mouse osteoblasts. Primary mouse calvarial osteoblasts were cultured and treated with various doses of IGF 1 before transfection with si RNA targeting the collagen type I alpha 2 ( Col1a2 ) or La ribonucleoprotein domain family member 6 ( Larp6 ) genes. Alkaline phosphatase ( ALP ) activity, osteocalcin staining, alizarin red quantification and the expression level of runt‐related transcription factor 2 ( RUNX 2) were performed to assess the differentiation of pre‐osteoblasts. Based on Western blot analysis, IGF 1 up‐regulated COL 1A2 protein expression in the primary osteoblasts in a dose‐ and time‐dependent manner. In addition, Col1a2 interference inhibited the differentiation and mineralization of osteoblasts. IGF 1 also stimulated the differentiation of mouse primary osteoblasts and increased LARP 6 expression during osteogenic differentiation. RNA ‐Immunoprecipitation ( IP ) indicated that LARP 6 could bind to Col1a2 mRNA after IGF 1 stimulation. However, transfection of Larp6 ‐specific si RNA significantly reduced collagen and ALP secretion, mineralization and inhibited the expression of osteocalcin and RUNX 2, indicating that Larp6 interference inhibited the differentiation ability of primary mouse calvarial osteoblasts, and these effects could not be reversed by IGF 1. Thus, IGF 1 could promote COL 1A2 expression and osteoblast differentiation in primary mouse calvarial pre‐osteoblasts by increasing LARP 6 expression via a posttranscriptional mechanism.