title: Effect of stem cell factor, interleukin-6, nitric oxide and transforming growth factor-beta on the osteoclast differentiation induced by 1 alpha,25-(OH)2D3 in primary murine bone marrow cultures.
abstract: Osteotropic hormones and cytokines are involved in the differentiation of osteoclast progenitors from haematopoietic stem cells to multinucleated osteoclasts which mediate bone resorption. Stem cell factor, interleukin-6, nitric oxide, and transforming growth factor-beta are implicated in the regulation of bone resorption by osteoclast. We test whether stem cell factor, interleukin-6, nitric oxide, and transforming growth factor-beta affect the generation of osteoclast-like multi-nucleated cells induced by 1 alpha,25-(OH)2D3. 1 alpha,25-(OH)2D3 increase the generation of osteoclast-like cells retaining osteoclast characteristics including multinuclearity and positive staining for tartrate-resistant acid phosphatase. Combined treatment of stem cell factor with interleukin-6 synergistically potentiates the ability of 1 alpha,25-(OH)2D3 to generate tartrate-resistant acid phosphatase-positive multinucleated cells. However, either stem cell factor or interleukin-6 alone does not induce the generation of tartrate-resistant acid phosphatase-positive multinucleated cells. Transforming growth factor-beta produces a biphasic effect on osteoclast generation induced by 1 alpha,25-(OH)2D3. Transforming growth factor-beta stimulates osteoclast generation at low concentration (0.1 ng/ml) whereas it suppresses the formation of osteoclast-like cell at higher concentration (1 ng/ml). Sodium nitroprusside, a donor of nitric oxide, almost completely inhibits the generation of 1 alpha,25-(OH)2D3-induced osteoclast at high concentration (100 microM), but it significantly enhances the osteoclast generation at low concentrations (3 microM). These results suggest that stem cell factor, interleukin-6, transforming growth factor-beta, and nitric oxide interact with 1 alpha,25-(OH)2D3 to modulate the differentiation of hematopoietic precursors toward committed osteoclast precursors.
authors.affiliation: Department of Dental Pharmacology, School of Dentistry, Wonkwang University, South Korea.
authors.forename: H J
authors.initials: HJ
authors.lastname: Chae
authors.forename: R K
authors.initials: RK
authors.lastname: Park
authors.forename: J S
authors.initials: JS
authors.lastname: Kang
authors.forename: H S
authors.initials: HS
authors.lastname: Shin
authors.forename: S C
authors.initials: SC
authors.lastname: Kim
authors.forename: H T
authors.initials: HT
authors.lastname: Chung
authors.forename: D W
authors.initials: DW
authors.lastname: Son
authors.forename: K I
authors.initials: KI
authors.lastname: Ko
authors.forename: J B
authors.initials: JB
authors.lastname: Kim
authors.forename: Y C
authors.initials: YC
authors.lastname: Park
authors.forename: H R
authors.initials: HR
authors.lastname: Kim
mesh_terms: D015650:24,25-Dihydroxyvitamin D 3 / Q000494:pharmacology*; D000818:Animals; D001854:Bone Marrow Cells / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured / Q000378:metabolism; D015850:Interleukin-6 / Q000378:metabolism*; D051379:Mice; D008813:Mice, Inbred ICR; D009569:Nitric Oxide / Q000378:metabolism*; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism*; D019089:Stem Cell Factor / Q000378:metabolism*; D016212:Transforming Growth Factor beta / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; D019089:Stem Cell Factor; D016212:Transforming Growth Factor beta; D009569:Nitric Oxide; D015650:24,25-Dihydroxyvitamin D 3