Transient overexpression of sonic hedgehog alters the architecture and mechanical properties of trabecular bone. Academic Article uri icon

Overview

MeSH

  • Animals
  • Bone Remodeling
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Parathyroid Hormone
  • Parathyroid Hormone-Related Protein
  • Polymerase Chain Reaction

MeSH Major

  • 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.

publication date

  • September 2009

has subject area

  • Animals
  • Bone Remodeling
  • Bone and Bones
  • Hedgehog Proteins
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Parathyroid Hormone
  • Parathyroid Hormone-Related Protein
  • Polymerase Chain Reaction

Research

keywords

  • Journal Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3276343

Digital Object Identifier (DOI)

  • 10.1359/jbmr.090313

PubMed ID

  • 19338448

Additional Document Info

start page

  • 1598

end page

  • 1607

volume

  • 24

number

  • 9