PMID- 16750176 OWN - NLM STAT- MEDLINE DCOM- 20060822 LR - 20240109 IS - 0006-2952 (Print) IS - 0006-2952 (Linking) VI - 72 IP - 2 DP - 2006 Jul 14 TI - Attenuation of osteoclastogenesis and osteoclast function by apigenin. PG - 184-97 AB - The physiological effects of the flavone, apigenin on bone cells were studied. We first show that apigenin inhibits tumor necrosis factor alpha (TNFalpha)- and interferon gamma (IFNgamma)-induced secretion of several osteoclastogenic cytokines from MC3T3-E1 mouse calvarial osteoblast cell line. Ligands of the TNF receptor family constitute the most potent osteoclastic cytokines. In MC3T3-E1 cells, apigenin dose-dependently (from 5 to 20 microM) inhibits TNFalpha-induced production of the osteoclastogenic cytokines, IL-6 (interleukin-6), RANTES (regulated upon activation, normal T cell-expressed and -secreted), monocyte chemoattractant protein-1 (MCP-1) and MCP-3. In addition, apigenin inhibits IFNgamma-stimulated secretion of monokines, CXCL-9, and -10 in MC3T3-E1 cells. Next, we show that apigenin strongly inhibits differentiation of 3T3-L1 preadipocytes to adipocytes with attendant inhibition of adipocyte differentiation-induced IL-6, MCP-1, and leptin production. Inhibition of adipogenic differentiation by apigenin could be due to induction of osteogensis as it robustly upregulates mRNA levels of bone morphogenetic protein-6 (BMP-6). Finally, the presence of apigenin inhibited osteoclast differentiation from the RAW 264.7 cell line by reducing receptor activator of nuclear factor kappa ligand (RANKL)-induced expression of tartrate-resistant acid phosphatase (TRAP), RANK, and calcitonin receptor but not CCR1, resulting in the inhibition of multinucleated osteoclast formation. Similarly, apigenin inhibited expression of the osteoclast differentiation markers TRAP, RANK, and c-Fms in osteoclast precursor cells obtained from mouse bone marrow following treatment with RANKL and macrophage colony stimulating factor (MCSF). Furthermore, apigenin induced apoptosis of mature osteoclasts obtained from rabbit long bone and inhibited bone resorption. In all instances, a structurally related compound, flavone had no significant effect. These data suggest that apigenin has multiple effects on all three bone cells that could prevent bone loss in vivo. FAU - Bandyopadhyay, Sanghamitra AU - Bandyopadhyay S AD - Genetics and Aging Research Unit, Psychiatry Department, Massachusetts General Hospital, Harvard Medical School, Charlestown, MA 02129, USA. FAU - Lion, Jean-Marc AU - Lion JM FAU - Mentaverri, Romuald AU - Mentaverri R FAU - Ricupero, Dennis A AU - Ricupero DA FAU - Kamel, Said AU - Kamel S FAU - Romero, Jose R AU - Romero JR FAU - Chattopadhyay, Naibedya AU - Chattopadhyay N LA - eng GR - AR02215/AR/NIAMS NIH HHS/United States GR - ES014462/ES/NIEHS NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural DEP - 20060429 PL - England TA - Biochem Pharmacol JT - Biochemical pharmacology JID - 0101032 RN - 0 (DNA Primers) RN - 0 (Tumor Necrosis Factor-alpha) RN - 7V515PI7F6 (Apigenin) RN - 82115-62-6 (Interferon-gamma) SB - IM MH - Animals MH - Apigenin/*pharmacology MH - Base Sequence MH - Cell Differentiation/drug effects MH - Cell Division/*drug effects MH - Cell Line MH - DNA Primers MH - Interferon-gamma/biosynthesis MH - Mice MH - Osteoclasts/cytology/*drug effects MH - Polymerase Chain Reaction MH - Tumor Necrosis Factor-alpha/biosynthesis EDAT- 2006/06/06 09:00 MHDA- 2006/08/23 09:00 CRDT- 2006/06/06 09:00 PHST- 2006/03/23 00:00 [received] PHST- 2006/04/17 00:00 [revised] PHST- 2006/04/17 00:00 [accepted] PHST- 2006/06/06 09:00 [pubmed] PHST- 2006/08/23 09:00 [medline] PHST- 2006/06/06 09:00 [entrez] AID - S0006-2952(06)00251-6 [pii] AID - 10.1016/j.bcp.2006.04.018 [doi] PST - ppublish SO - Biochem Pharmacol. 2006 Jul 14;72(2):184-97. doi: 10.1016/j.bcp.2006.04.018. Epub 2006 Apr 29.