EFFECT OF STEM-CELL FACTOR, INTERLEUKIN-6, NITRIC-OXIDE AND TRANSFORMING-GROWTH-FACTOR-BETA ON THE OSTEOCLAST DIFFERENTIATION-INDUCED BY 1-ALPHA,25-(OH)(2)D-3 IN PRIMARY MURINE BONE-MARROW CULTURES

Osteotropic hormones and cytokines are involved in the differentiation of osteoclast progenitors from haematopoietic stem cells to multinucl eated osteoclasts which mediate bone resorption. Stem cell factor, int erleukin-6, nitric oxide, and transforming growth factor-beta are impl icated in the regulation of bone resorption by osteoclast. We test whe ther stem cell factor, interleukin-6, nitric oxide, and transforming g rowth factor-beta affect the generation of osteoclast-like multinuclea ted cells induced by 1 alpha 25-(OH)(2)D-3. 1 alpha 25-(OH)(2)D-3 incr eases the generation of osteoclast-like cells retaining osteoclast cha racteristics including multinuclearity and positive staining for tartr ate-resistant acid phosphatase. Combined treatment of stem cell factor with interleukin-6 synergistically potentiates the ability of 1 alpha ,25-(OH)(2)D-3 to generate tartrate-resistant acid phosphatase-positiv e multinucleated cells. However, either stem cell factor or interleuki n-6 alone does not induce the generation of tartrate resistant acid ph osphatase-positive multinucleated cells. Transforming growth factor-be ta produces a biphasic effect on osteoclast generation induced by 1 al pha,25-(OH)(2)D-3. Transforming growth factor-beta stimulates osteocla st generation at low concentration (0.1 ng/ml) whereas it suppresses t he formation of osteoclast-like cell at higher concentration (1 ng/ml) . Sodium nitroprusside, a donor of nitric oxide. almost completely inh ibits the generation of 1 alpha,25(OH)(2)D-3-induced osteoclast at hig h concentration (100 mu M), but it significantly enhances the osteocla st generation at low concentrations (3 mu M). These results suggest th at stem cell factor, interleukin-6, transforming growth factor-beta, a nd nitric oxide interact with 1 alpha,25-(OH)(2)D-3 to modulate the di fferentiation of hematopoietic precursors toward committed osteoclast precursors.