ROLE OF NEUROPEPTIDEY IN THE SYMPATHETIC NERVE REGULATION OF BONE METABOLISM

在这个项目中，我们展示了神经肽Y(NPY)在神经调节骨代谢中的生理作用。神经肽Y是周围交感神经纤维中与去甲肾上腺素共同传递的物质。观察神经肽Y对β-肾上腺素能受体(β-AR)激动剂异丙肾上腺素诱导的小鼠骨髓细胞破骨细胞分化的影响。小鼠骨髓细胞结构性表达β-Y1受体和NPY-2-AR的mRNAs。NPY抑制异丙肾上腺素诱导的破骨细胞样细胞的形成，但不抑制1-α，25(OH)_2D_3和可溶性核因子B_K受体激活剂(RANKL)诱导的破骨细胞样细胞的形成，抑制异丙肾上腺素增加的RANKL和cAMP(CAMP)的产生，但不抑制1α，25(OH)_2D_3诱导的破骨细胞生成。NPY也抑制腺苷环化酶激活剂Forsklin诱导的破骨细胞生成，但不抑制外源性供应的二丁基环腺苷类似物诱导的破骨细胞生成。这些结果表明，NPY通过阻断激动剂诱导的小鼠骨髓细胞cAMP和RANKL的生成而抑制异丙肾上腺素诱导的破骨细胞生成，提示NPY与β-AR激动剂在骨吸收中存在相互作用。

In this project, we demonstrated a physiological role of neuropeptide Y (NPY), a co-transmitter with noradrenaline in peripheral sympathetic nerve fibers, in the nerve regulation of bone metabolism. The effect of NPY on the osteoclastogenesis in mouse bone marrow cell cultures treated with isoprenaline, a β-adrenergic receptor (β-AR) agonist, was examined. The mouse bone marrow cells constitutively expressed mRNAs for the NPY-Y1 receptor and β2-AR. NPY inhibited the formation of osteoclast-like cells induced by isoprenaline but not that by 1α, 25-dihydroxyvitamin D_3 (1a, 25(OH)_2D_3) or soluble receptor activator of nuclear factor-B_K ligand (RANKL); and it suppressed the production of RANKL and cyclic AMP (cAMP) increased by isoprenaline but not those increased by 1α, 25(OH)_2D_3. NPY also inhibited osteoclastogenesis induced by forskolin, an activator of adenylate cyclase; however, it did not inhibit that induced by exogenously supplied dibutyryl cAMP, a cell-permeable cAMP analog that activates cAMP-dependent protein kinase. These results demonstrate that NPY inhibited the isoprenaline-induced osteoclastogenesis by blocking the agonist-elicited increases in the production of cAMP and RANKL in mouse bone marrow cells, suggesting an interaction between NPY and β-AR agonist in bone resorption.