Absence of platelet-activating factor receptor protects mice from osteoporosis following ovariectomy

The Journal of Clinical Investigation
Hisako HikijiTakao Shimizu

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, ...Continue Reading

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Citations

Sep 21, 2005·The Journal of Experimental Medicine·Yasuyuki KiharaTakao Shimizu
Aug 16, 2012·Biochimica Et Biophysica Acta·Stephen M SimsS Jeffrey Dixon
Jan 12, 2008·Progress in Lipid Research·Hisako HikijiSatoshi Ishii
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Methods Mentioned

BETA
hormone replacement therapy
Protein Assay
electrophoresis
PCR
light microscopy

Software Mentioned

Photoshop
StatView

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