Transient overexpression of Sonic hedgehog alters the architecture and mechanical properties of trabecular bone

Maija Ht Kiuru, Jason Solomon, Bassem Ghali, Marjolein Van Der Meulen, Ronald G. Crystal, Chisa Hidaka

Research output: Contribution to journalArticle

11 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1598-1607
Number of pages10
JournalJournal of Bone and Mineral Research
Volume24
Issue number9
DOIs
StatePublished - 2009
Externally publishedYes

Keywords

  • Adenovirus
  • Bone remodeling
  • Hedgehog
  • Osteoblasts
  • Osteoclasts

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism

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