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

本文研究了神经肽P物质（SP）对骨代谢的影响。免疫细胞化学研究表明，SP免疫反应阳性神经纤维位于骨表面附近，SP受体神经激肽1受体（NK_1-Rs）分布于成骨细胞、破骨细胞和骨细胞表面，反复加入SP可引起骨吸收增加，而单独加入SP对骨吸收无影响。与SP拮抗剂或NK_1-R拮抗剂共同孵育可抑制SP引起的骨吸收增加。在成骨细胞中，14天培养的成骨细胞中有NK_1-R的mRNA表达，4天培养的成骨细胞和大鼠成骨细胞中均无NK_1-R的mRNA表达;荧光标记的SP在成骨期与成骨细胞结合。SP和神经激肽B均能促进成骨细胞的骨形成，提示SP通过NK_1-R促进破骨细胞的分化和骨吸收活性，SP在成骨细胞表达NK_1-R后，在骨形成后期促进成骨细胞的骨形成。

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.