Sonic hedgehog is involved in osteoblast differentiation by cooperating with BMP‐2

Abstract

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 microg) into muscle of mice induced formation of ectopic bone, whereas transplantation of r-SHH-N (1-5 microg) failed to generate it. These results indicate that Shh plays important roles in osteoblast differentiation by cooperating with BMP.

Indian hedgehog positively regulates calvarial ossification and modulates bone morphogenetic protein signaling

“…These studies suggested that Ihh, and not Shh, is the central determinant of intramembranous calvarial ossification. However, it is curious that Shh has been well known to be a potent osteogenic factor in various cell types and model systems, both in vitro and in vivo (Jemtland et al, 2003;Nakamura et al, 1997;Yuasa et al, 2002). Keeping this in mind, we cannot exclude the possibility that Shh, to some extent, ameliorates the Ihh null mouse calvarial phenotype.…”

“…Although Hedgehog signaling (mediated by either Indian or Sonic) has been observed to enhance the osteogenic differentiation in numerous bone forming cells in vitro (Ho et al, 2007;James et al, 2010;Jemtland et al, 2003;Levi et al, 2011;Nakamura et al, 1997;Spinella-Jaegle et al, 2001;Yuasa et al, 2002;van der Horst et al, 2003;Wu et al, 2004;Zunich et al, 2009), the precise effects of Ihh in calvarial ossification have not been yet defined. Toward this end, Abzhanov et al studied Ihh misexpression in chick and mouse calvaria.…”

Prostate Cancer Cells and Bone Stromal Cells Mutually Interact with Each Other through Bone Morphogenetic Protein-mediated Signals

“…SHH initiates the expression of Bmp2 in the mesoderm (31). During osteogenesis and chondrogenesis, SHH alters the response of cells to BMPs (32,33). SHH has been reported to facilitate BMP-2-mediated Smad1 activation in osteoblasts (34).…”

A Perspective: Engineering Periosteum for Structural Bone Graft Healing

“…Thus, improving the efficacy of BMP treatment and searching for alternative osteogenic factors or genes have become the most important topics in bone regeneration therapy. Cooperation of two or multiple pathways to promote bone formation in a tissue-engineering application has not yet been fully explored and is fertile ground for future investigation [58,99].…”