Pertussis toxin inhibits hormonal stimulation of bone resorption in fetal rat limb bones

The cellular basis for hormonal control of bone resorption is poorly understood. As the identifiable receptors for bone resorbing agents such as parathyroid hormone (PTH) and 1,25-dihydroxyvitamin D₃ [1,25(OH)₂D₃] are located on osteoblasts rather than osteoclasts, the nature of cellular signaling is obscure. Here it is reported that exposure of fetal rat limb bones to pertussis toxin, a bacterial protein that inhibits certain GTP binding proteins (G-proteins) involved in signal transduction, markedly inhibits bone resorption elicited by PTH, 1,25(OH)₂D₃ and prostaglandin E₂. Pertussis toxin does not block the inhibition of alkaline phosphatase activity by PTH or 1,25(OH)₂D₃, and it potentiates the cyclic AMP response to PTH. These data support the existence of a pertussis toxin-sensitive G-protein that participates in regulation of bone resorption. The putative G-protein is apparently not involved in the initial transduction of hormonal signals, but it may be part of a final common pathway through which the osteolast is activated by agents with widely divergent initial actions.