Parathyroid hormone-regulated production of stem cell factor in human osteoblasts and osteoblast-like cells

We investigated stem cell factor (SCF) expression in osteoblasts because ma st cells, which occur ectopically in hyperparathyroid bone, are induced by SCF. Nontransformed osteoblasts and Saos2 or MG63 cells expressed SCF in re sponse to PTH. Western analysis showed only large, cell-associated isoforms , M(r)s similar to 40-48 kD. Transfection of MG63 cells with plasmids expre ssing antisense SCF mRNA eliminated immunoreactive SCF. Sequencing osteobla st SCF cDNAs showed that exon 6 was omitted. mRNAs without exon 6 produce m embrane-associated SCF isoforms in rodents, suggesting that human SCFs are processed similarly. The major osteoblastic SCF mRNA, similar to 5 kB, was augmented by PTH. Neither protein or mRNA was increased by vitamin D, howev er, 6-7 kB transcripts were predominant in other tissues but not detectable in osteoblasts. We conclude that osteoblasts express SCF in response to PT H, with mRNA and protein processing differences relative to other cells. SC F stimulates osteoclasts, suggesting that PTH-induced osteoblastic SCF func tions to accelerate bone turnover. Mast cells may occur due to SCF overexpr ession at extreme PTH levels. (C) 1999 Academic Press.