Osteoblast specific Y1 receptor deletion enhances bone mass.
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.
Neuroscience Program, Garvan Institute of Medical Research, Darlinghurst, Sydney, New South Wales, Australia.
Nicola J
NJ
Lee
Amy D
AD
Nguyen
Ronaldo F
RF
Enriquez
Kharen L
KL
Doyle
Amanda
A
Sainsbury
Paul A
PA
Baldock
Herbert
H
Herzog
D050154:Adiposity / Q000235:genetics; D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D001842:Bone and Bones / Q000033:anatomy & histology* / Q000166:cytology / Q000000981:diagnostic imaging / Q000201:enzymology; D002454:Cell Differentiation / Q000235:genetics; D003720:Densitometry; D016326:Extracellular Matrix Proteins / Q000235:genetics / Q000378:metabolism; D017353:Gene Deletion; D051379:Mice; D009929:Organ Size; D009928:Organ Specificity; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology; D017476:Receptors, Neuropeptide Y / Q000172:deficiency* / Q000235:genetics; D015854:Up-Regulation / Q000235:genetics; D055114:X-Ray Microtomography
D015415:Biomarkers; C513308:Dmp1 protein, mouse; D016326:Extracellular Matrix Proteins; D017476:Receptors, Neuropeptide Y; C097212:neuropeptide Y-Y1 receptor; D015675:Osteocalcin; D000469:Alkaline Phosphatase