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Sonic hedgehog is involved in osteoblast differentiation by cooperating with BMP‐2
Author(s) -
Yuasa Takahito,
Kataoka Hiroko,
Kinto Naoki,
Iwamoto Masahiro,
EnomotoIwamoto Motomi,
Iemura Shunichiro,
Ueno Naoto,
Shibata Yasuaki,
Kurosawa Hisashi,
Yamaguchi Akira
Publication year - 2002
Publication title -
journal of cellular physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.529
H-Index - 174
eISSN - 1097-4652
pISSN - 0021-9541
DOI - 10.1002/jcp.10166
Subject(s) - osteoblast , sonic hedgehog , osteocalcin , bone morphogenetic protein , bone morphogenetic protein 2 , chemistry , microbiology and biotechnology , alkaline phosphatase , endocrinology , medicine , bone morphogenetic protein 7 , hedgehog signaling pathway , cellular differentiation , biology , in vitro , signal transduction , biochemistry , gene , enzyme
The roles of Sonic hedgehog ( Shh ) and Bone morphogenetic protein‐2 ( Bmp‐2 ) in osteoblast differentiation were investigated using in vitro cell systems. Recombinant amino‐terminal portion of SHH (rSHH‐N) dose dependently stimulated ALP activity in C3H10T1/2 and MC3T3‐E1 cells. rSHH‐N induced expression of Osteocalcin mRNA in C3H10T1/2 cells. A soluble form of the receptor for type IA BMP receptor antagonized rSHH‐N‐induced ALP activity in C3H10T1/2 and MC3T3‐E1 cells, indicating that BMPs are involved in SHH‐induced osteoblast differentiation. Simultaneous supplement with rSHH‐N and BMP‐2 synergistically induced ALP activity and expression of Osteocalcin mRNA in C3H10T1/2 cells. Pretreatment with rSHH‐N for 6 h enhanced the response to BMP‐2 by increasing ALP activity in C3H10T1/2 and MC3T3‐E1 cells. Stimulatory effects of rSHH‐N and additive effects with rSHH‐N and BMP‐2 on ALP activity were also observed in mouse primary osteoblastic cells. Transplantation of BMP‐2 (1 μg) into muscle of mice induced formation of ectopic bone, whereas transplantation of r‐SHH‐N (1–5 μg) failed to generate it. These results indicate that Shh plays important roles in osteoblast differentiation by cooperating with BMP. © 2002 Wiley‐Liss, Inc.