Osteoblast specific Y1 receptor deletion enhances bone mass

Bone. 2011 Mar 1;48(3):461-7. doi: 10.1016/j.bone.2010.10.174. Epub 2010 Oct 30.

Abstract

Neuropeptide Y, Y1 receptors are found in neuronal as well as bone tissue and Y1 signalling has been implicated in the regulation of bone mass. However, the contribution of Y1 receptors located in these different tissues, particularly that of the bone-specific Y1 receptors, to the regulation of bone homeostasis is unclear. Here we demonstrate that osteoblast-specific Y1 receptor deletion resulted in a marked increase in femoral cancellous bone volume, trabecular thickness and trabecular number. This is the result of elevated osteoblast activity as shown by increased mineral apposition rate and bone formation rate, and is associated with an upregulation in the mRNA expression levels of alkaline phosphatase, osteocalcin and dentin matrix protein-1. Furthermore, osteoblastic Y1 receptor deletion also led to increased mineral apposition rate on both the endocortical and the periosteal surfaces resulting in increased femoral diameter. Together these data demonstrate a direct role for the Y1 receptor on osteoblasts in the regulation of osteoblast activity and bone formation in vivo and suggest that targeting Y1 receptor signalling directly in the bone may have potential therapeutic implications for stimulating bone accrual in diseases such as osteoporosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adiposity / genetics
  • Alkaline Phosphatase / genetics
  • Alkaline Phosphatase / metabolism
  • Animals
  • Biomarkers / metabolism
  • Bone and Bones / anatomy & histology*
  • Bone and Bones / cytology
  • Bone and Bones / diagnostic imaging
  • Bone and Bones / enzymology
  • Cell Differentiation / genetics
  • Densitometry
  • Extracellular Matrix Proteins / genetics
  • Extracellular Matrix Proteins / metabolism
  • Gene Deletion*
  • Mice
  • Organ Size
  • Organ Specificity
  • Osteoblasts / cytology
  • Osteoblasts / metabolism*
  • Osteocalcin / genetics
  • Osteocalcin / metabolism
  • Osteogenesis / physiology
  • Receptors, Neuropeptide Y / deficiency*
  • Receptors, Neuropeptide Y / genetics
  • Up-Regulation / genetics
  • X-Ray Microtomography

Substances

  • Biomarkers
  • Dmp1 protein, mouse
  • Extracellular Matrix Proteins
  • Receptors, Neuropeptide Y
  • neuropeptide Y-Y1 receptor
  • Osteocalcin
  • Alkaline Phosphatase