RRC ID 61226
Author Hikiji H, Ishii S, Shindou H, Takato T, Shimizu T.
Title Absence of platelet-activating factor receptor protects mice from osteoporosis following ovariectomy.
Journal J Clin Invest
Abstract While platelet-activating factor (PAF) is produced in various diseases associated with bone resorption, its functions in bone metabolism remain unknown. Using PAF receptor-deficient mice, we evaluated the role of PAF in the development of bone resorption following ovariectomy, a model of postmenopausal osteoporosis. Through observations of bone mineral density and histomorphometric parameters, it was found that bone resorption was markedly attenuated in PAF receptor-deficient mice, indicating that PAF links estrogen depletion and osteoporosis in vivo. Osteoclasts expressed higher amounts of the enzymes required for PAF biosynthesis than osteoblasts. TNF-alpha and IL-1beta increased the acetyl-coenzyme A:lyso-PAF acetyltransferase activity in osteoclasts. Osteoclasts, but not osteoblasts, expressed the functional PAF receptor. PAF receptor stimulation prolonged the survival of osteoclasts in vitro. Furthermore, osteoclasts treated with a PAF receptor antagonist, and also those from PAF receptor-deficient mice, showed reductions in survival rate and Ca resorption activity. Consistently, in organ cultures, bone resorption was significantly suppressed by a PAF receptor antagonist treatment or genetic PAF receptor deficiency. Thus, these results suggest that, through the inflammatory cytokines, estrogen depletion enhances PAF production as a unique autocrine factor for osteoclast functions. Inhibition of PAF function might pave the way for a new strategy to prevent postmenopausal bone loss without disturbing osteoblast functions.
Volume 114(1)
Pages 85-93
Published 2004-7-1
DOI 10.1172/JCI20504
PMID 15232615
PMC PMC437965
MeSH Animals Bone Resorption / prevention & control Disease Models, Animal Female Mice Mice, Knockout Osteoporosis / etiology Osteoporosis / prevention & control* Ovariectomy / adverse effects* Platelet Membrane Glycoproteins / deficiency* Platelet Membrane Glycoproteins / genetics Platelet Membrane Glycoproteins / physiology* Receptors, G-Protein-Coupled / deficiency* Receptors, G-Protein-Coupled / genetics Receptors, G-Protein-Coupled / physiology*
IF 11.864
Human and Animal Cells MC3T3-E1(RCB1126)