Study for the modulation of bone metabolism by a neuropeptide, substance P.

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We studied the effects of neuropeptide, substance P (SP) on the bone metabolism. By the immunocytochemical studies indicated that SP-immunoreactive nerve fibers were located close to the bone surface, and that the SP receptors, neurokinin- 1 receptors (NK_1-Rs), were exhibited on the surfaces of osteoblasts, osteoclasts, and osteocytes.The repetition of the addition of SP induced the increase of osteoclastic bone resorption, but single addition of SP caused no effects. The increased bone resorption by SP was inhibited by the co-incubation with SP-antagonist or NK_1-R antagonist. Furthermore, the differentiation from blood monocytes to osteoclasts was stimulated by the addition of SP.Regarding with osteoblasts, mRNA of NK_1-R was expressed in 14-day cultured osteoblasts, but not in 4-day cultured osteoblasts nor rat osteoblastic cell ; Ros. Fluorescence labeled SP was bind with the osteoblasts at the bone-formation stage. The addition of SP and neurokinin B induced the increase of bone formation.These results indicated that SP stimulates the differentiation and bone resorption activity of osteoclasts through the NK_1-R, and that SP stimulated the bone formation of osteoblast at the late stage of bone formation after expression of NK_1-R on osteoblasts.