Publication Type	Academic Article
Authors	Kiuru M, Solomon J, Ghali B, van der Meulen M, Crystal R, Hidaka C
Journal	J Bone Miner Res
Volume	24
Issue	9
Pagination	1598-607
Date Published	09/01/2009
ISSN	1523-4681
Keywords	Bone and Bones, Hedgehog Proteins
Abstract	Bone formation and remodeling involve coordinated interactions between osteoblasts and osteoclasts through signaling networks involving a variety of molecular pathways. We hypothesized that overexpression of Sonic hedgehog (Shh), a morphogen with a crucial role in skeletal development, would stimulate osteoblastogenesis and bone formation in adult animals in vivo. Systemic administration of adenovirus expressing the N-terminal form of Shh into adult mice resulted in a primary increase in osteoblasts and their precursors. Surprisingly, however, this was associated with altered trabecular morphology, decreased bone volume, and decreased compressive strength in the vertebrae. Whereas no change was detected in the number of osteoclast precursors, bone marrow stromal cells from Shh-treated mice showed enhanced osteoclastogenic potential in vitro. These effects were mediated by the PTH/PTH-related protein (PTHrP) pathway as evidenced by increased sensitivity to PTH stimulation and upregulation of the PTH/PTHrP receptor (PPR). Together, these data show that Shh has stimulatory effects on osteoprogenitors and osteoblasts in adult animals in vivo, which results in bone remodeling and reduced bone strength because of a secondary increase in osteoclastogenesis.
DOI	10.1359/jbmr.090313
PubMed ID	19338448
PubMed Central ID	PMC3276343