Expression of stem cell factor by osteoblasts in normal and hyperparathyroid bone: relation to ectopic mast cell differentiation

Abstract 

Mast cells accumulate in hyperparathyroid bone, but the reason is not clear. We compared the distribution of mast cells and related growth factors in normal and hyperparathyroid bone. Mast cell formation was strongly affected by proximity to bone-forming surfaces of hyperparathyroid bone. Hyperparathyroidism greatly increased the production by active, bone-synthesizing osteoblasts of stem cell factor (SCF) but not of IL-3. Osteoblast SCF was distributed to the basolateral cell membranes, and its cDNA sequence (GenBank AF119835) is homologous to the murine membrane-bound SCF. Quiescent osteoblasts did not produce detectable SCF. Synthetic osteoblasts in normal bone were SCF positive, but comprised a much smaller population of cells, in keeping with the slow turnover of normal bone. Major SCF isoforms on immunoblot analysis of osteoblast-fraction proteins from high-turnover bone had M_rs of about 48 and 40 kDa. Similar SCF isoforms were produced by MG63 osteoblast-derived cells and were identified by several anti-SCF antibodies. SCF is expressed in several mesenchymal cell types in a complementary fashion with cells bearing its receptor. SCF potently facilitates differentiation of mast cells, so the increase in paratrabecular mast cells in hyperparathyroid bone is probably driven by osteoblastic SCF. However, since mast cells are not normal components of bone, osteoblastic SCF probably regulates other cells, with mast cell differentiation occurring as a side effect greatly increased osteoblastic activity.