Substance P stimulates the Formation of Osteoclasts from Human Peripheral Blood Monocytes

Osteoclasts, the multinucleated giant cells that resorb bone, develop from hematopoietic cells of the monocyte-macrophage lineage. Osteoclasts precursors that posess receptor activator of neuclear factor kappa B (RANK) recognize RANK ligand (RANKL) and differentiate into osteoclasts in the presence of macrophage colony stimulating factor (M-CSF). The purpose of this study is to investigate the effects of neuropeptide substance P (SP) on the formation of osteoclasts from human peripheral blood monocytes (PBMC) in the presence of RANKL and M-CSF. Fluorecent immunostaining using specific antibody against neurokinin-1 receptor (NK_1-R) indicated the localization of punctuate distribution of NK1-R on the PBMC. PBMC cultured with 10% FBS containing 1, 25(OH)_2D_3, M-CSF, RANKL for 2 weeks formed TRAP (+) mononucleated cells and TRAP (+) multinucleated cells. The addition of 10^〜10^ M SP induced the increased number of TRAP (+) mononucleated cells and TRAP (+) multinucleated cells. The increase of TRAP (+) mononucleated cells and TRAP (+) multinucleated by SP was inhibited by the addition of spantide, SP antagonist or FK224, NK_1-R. These findings suggest that SP stimulated the formation of osteoclast precursors from PBMC and the formation of osteoclasts through the NK_1-Rs.