PMID- 11344046 OWN - NLM STAT- MEDLINE DCOM- 20010809 LR - 20190906 IS - 8756-3282 (Print) IS - 1873-2763 (Linking) VI - 28 IP - 5 DP - 2001 May TI - Tumor necrosis factor-alpha cooperates with receptor activator of nuclear factor kappaB ligand in generation of osteoclasts in stromal cell-depleted rat bone marrow cell culture. PG - 474-83 AB - A member of the tumor necrosis factor (TNF) family, receptor activator of nuclear factor kappaB ligand (RANKL; also known as ODF, OPGL, and TRANCE), plays critical roles in osteoclast differentiation and activation in the presence of macrophage colony-stimulating factor (M-CSF). Recently, TNF-alpha has also been shown to induce the formation of multinucleated osteoclast-like cells (MNCs) in the presence of M-CSF from mouse macrophages. We demonstrated that mononuclear preosteoclast-like cells (POCs) were formed in the presence of conditioned medium of osteoblastic cells in a rat bone marrow culture depleted of stromal cells. Using this culture system, in this study we examined whether TNF-alpha affects differentiation into POCs from hematopoietic progenitor cells. Human TNF-alpha (hTNF-alpha) markedly stimulated the formation of POCs. Moreover, a concentration as low as 0.005 ng/mL of hTNF-alpha increased the level of mRNA for calcitonin receptor (CTR) and cathepsin-K of POCs. The POCs induced by hTNF-alpha formed MNCs, which showed dentine-resorbing activity after coculture with primary osteoblasts. Stimulation was observed after 24 h of treatment with hTNF-alpha only on day 1 or day 2 of the culture. After 24 h of hTNF-alpha treatment, expression of the receptor activator of nuclear factor kappaB (RANK) mRNA was markedly increased. The addition of soluble RANKL (sRANKL) to the preformed POCs efficiently induced MNCs. Interestingly, treatment of bone marrow cells with hTNF-alpha and sRANKL synergistically augmented the formation of MNCs. This formation was abolished by the addition of human osteoprotegerin (hOPG). These results suggest that cooperation of TNF-alpha and RANKL is important for osteoclastogenesis. FAU - Komine, M AU - Komine M AD - Department of Microbiology, Saga Medical School, 5-1-1 Nabeshima, Saga 849-8501, Japan. FAU - Kukita, A AU - Kukita A FAU - Kukita, T AU - Kukita T FAU - Ogata, Y AU - Ogata Y FAU - Hotokebuchi, T AU - Hotokebuchi T FAU - Kohashi, O AU - Kohashi O LA - eng PT - Journal Article PL - United States TA - Bone JT - Bone JID - 8504048 RN - 0 (Carrier Proteins) RN - 0 (Culture Media, Conditioned) RN - 0 (Glycoproteins) RN - 0 (Membrane Glycoproteins) RN - 0 (Osteoprotegerin) RN - 0 (RANK Ligand) RN - 0 (RNA, Messenger) RN - 0 (Receptor Activator of Nuclear Factor-kappa B) RN - 0 (Receptors, Calcitonin) RN - 0 (Receptors, Cytoplasmic and Nuclear) RN - 0 (Receptors, Tumor Necrosis Factor) RN - 0 (TNFRSF11A protein, human) RN - 0 (TNFRSF11B protein, human) RN - 0 (TNFSF11 protein, human) RN - 0 (Tnfrsf11a protein, mouse) RN - 0 (Tnfrsf11b protein, mouse) RN - 0 (Tnfrsf11b protein, rat) RN - 0 (Tnfsf11 protein, mouse) RN - 0 (Tumor Necrosis Factor-alpha) RN - EC 3.4.- (Cathepsins) SB - IM MH - Animals MH - Bone Marrow Cells/cytology/drug effects/metabolism MH - Bone Remodeling/drug effects/*physiology MH - Bone and Bones/cytology/drug effects/metabolism MH - Carrier Proteins/genetics/*metabolism/pharmacology MH - Cathepsins/genetics MH - Cell Differentiation/drug effects/*physiology MH - Cells, Cultured/cytology/drug effects/metabolism MH - Coculture Techniques MH - Culture Media, Conditioned/pharmacology MH - Drug Interactions/*physiology MH - Glycoproteins/metabolism/pharmacology MH - Hematopoietic Stem Cells/cytology/drug effects/*metabolism MH - Male MH - Membrane Glycoproteins/genetics/*metabolism/pharmacology MH - Osteoblasts/cytology/drug effects/metabolism MH - Osteoclasts/cytology/drug effects/*metabolism MH - Osteoprotegerin MH - RANK Ligand MH - RNA, Messenger/drug effects/metabolism MH - Rats MH - Rats, Sprague-Dawley MH - Receptor Activator of Nuclear Factor-kappa B MH - Receptors, Calcitonin/genetics MH - Receptors, Cytoplasmic and Nuclear/metabolism MH - Receptors, Tumor Necrosis Factor MH - Stromal Cells/cytology/metabolism MH - Tumor Necrosis Factor-alpha/*metabolism/pharmacology EDAT- 2001/05/10 10:00 MHDA- 2001/08/10 10:01 CRDT- 2001/05/10 10:00 PHST- 2001/05/10 10:00 [pubmed] PHST- 2001/08/10 10:01 [medline] PHST- 2001/05/10 10:00 [entrez] AID - S8756328201004203 [pii] AID - 10.1016/s8756-3282(01)00420-3 [doi] PST - ppublish SO - Bone. 2001 May;28(5):474-83. doi: 10.1016/s8756-3282(01)00420-3.