PMID- 26303404 OWN - NLM STAT- MEDLINE DCOM- 20170925 LR - 20181202 IS - 1873-4847 (Electronic) IS - 0955-2863 (Linking) VI - 26 IP - 11 DP - 2015 Nov TI - n-3 polyunsaturated fatty acids stimulate osteoclastogenesis through PPARgamma-mediated enhancement of c-Fos expression, and suppress osteoclastogenesis through PPARgamma-dependent inhibition of NFkB activation. PG - 1317-27 LID - S0955-2863(15)00156-4 [pii] LID - 10.1016/j.jnutbio.2015.06.007 [doi] AB - n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have been reported to suppress osteoclastogenesis in vivo. In this study, the effect of PUFAs on receptor for activation of nuclear factor-kappaB ligand (RANKL)-induced osteoclastogenesis was examined using bone marrow-derived monocytes/macrophage precursor cells (BMMs) or bone marrow cells (BMCs) in vitro. EPA and DHA stimulated the osteoclastic differentiation of BMMs, but n-6 PUFAs, linoleic acid and arachidonic acid had no effect. The stimulation of osteoclastogenesis of BMMs by EPA and DHA was associated with enhancement of the gene expressions of c-Fos, tartrate-resistant acid phosphatase, cathepsin K and peroxisome proliferator-activated receptor-gamma (PPARgamma) and the protein levels of c-Fos, PPARgamma and nuclear factor of activated T cells, cytoplasmic, calcineurin-dependent-1 (NFATc1). The PPARgamma agonists, rosiglitazone and GW1929, also stimulated the osteoclastogenesis of BMMs. The PPARgamma antagonists, T0070907 and GW9662, inhibited the stimulations of osteoclastogenesis and c-Fos expression by EPA or DHA. However, EPA and DHA inhibited the osteoclastogenesis in BMCs including BMMs and mesenchymal stem cells (MSCs). This inhibition was associated with suppression of the expression of RANKL and nuclear factor-kappaB (NFkappaB)-regulating genes, cyclooxygenase 2, TNFalpha and IL-6 in BMCs and MSCs. The agonists and antagonists of PPARgamma showed that the inhibitions of NFkappaB transcriptional activity and osteoclastogenesis by EPA and DHA were PPARgamma-dependent. These results suggest that EPA and DHA directly act on BMMs and stimulate osteoclastogenesis through enhancing c-Fos expression mediated by PPARgamma but suppress osteoclastogenesis through the PPARgamma-dependent inhibition of NFkappaB activation of MSCs in BMCs. CI - Copyright (c) 2015 Elsevier Inc. All rights reserved. FAU - Nakanishi, Atsuko AU - Nakanishi A AD - Department of Food Science and Nutrition, Nara Women's University, Kita-uoya Nishi-machi, Nara, 630-8506, Japan. FAU - Tsukamoto, Ikuyo AU - Tsukamoto I AD - Department of Food Science and Nutrition, Nara Women's University, Kita-uoya Nishi-machi, Nara, 630-8506, Japan; Faculty of Clinical Nutrition, Hiroshima International University, 5-1-1, Hirokoshingai, Kure, Hiroshima, 737-0112, Japan. Electronic address: itsuka@cc.nara-wu.ac.jp. LA - eng PT - Journal Article DEP - 20150726 PL - United States TA - J Nutr Biochem JT - The Journal of nutritional biochemistry JID - 9010081 RN - 0 (Benzophenones) RN - 0 (Fatty Acids, Omega-3) RN - 0 (NF-kappa B) RN - 0 (NFATC1 protein, rat) RN - 0 (PPAR gamma) RN - 0 (Proto-Oncogene Proteins c-fos) RN - 0 (Thiazolidinediones) RN - 0 (Transcription Factors) RN - 05V02F2KDG (Rosiglitazone) RN - 25167-62-8 (Docosahexaenoic Acids) RN - 42HK56048U (Tyrosine) RN - AAN7QOV9EA (Eicosapentaenoic Acid) RN - EC 1.14.99.1 (Cyclooxygenase 2) RN - EC 1.14.99.1 (Ptgs2 protein, rat) RN - X8S066WKF4 (GW 1929) SB - IM EIN - J Nutr Biochem. 2016 Apr;30:189 MH - Animals MH - Benzophenones/pharmacology MH - Bone Marrow Cells/cytology/drug effects/physiology MH - Cells, Cultured MH - Cyclooxygenase 2/genetics/metabolism MH - Docosahexaenoic Acids/pharmacology MH - Eicosapentaenoic Acid/pharmacology MH - Fatty Acids, Omega-3/*pharmacology MH - Gene Expression Regulation/drug effects MH - Male MH - Mesenchymal Stem Cells/drug effects MH - NF-kappa B/*metabolism MH - Osteogenesis/*drug effects/genetics MH - PPAR gamma/agonists/antagonists & inhibitors/genetics/*metabolism MH - Proto-Oncogene Proteins c-fos/genetics/*metabolism MH - Rats, Wistar MH - Rosiglitazone MH - Thiazolidinediones/pharmacology MH - Transcription Factors/genetics/metabolism MH - Tyrosine/analogs & derivatives/pharmacology OTO - NOTNLM OT - Bone marrow-derived monocytes/macrophage precursor cells (BMMs) OT - Docosahexaenoic acid (DHA) OT - Eicosapentaenoic acid (EPA) OT - Osteoclastogenesis OT - PPARgamma OT - c-fos EDAT- 2015/08/26 06:00 MHDA- 2017/09/26 06:00 CRDT- 2015/08/26 06:00 PHST- 2015/01/27 00:00 [received] PHST- 2015/06/17 00:00 [revised] PHST- 2015/06/17 00:00 [accepted] PHST- 2015/08/26 06:00 [entrez] PHST- 2015/08/26 06:00 [pubmed] PHST- 2017/09/26 06:00 [medline] AID - S0955-2863(15)00156-4 [pii] AID - 10.1016/j.jnutbio.2015.06.007 [doi] PST - ppublish SO - J Nutr Biochem. 2015 Nov;26(11):1317-27. doi: 10.1016/j.jnutbio.2015.06.007. Epub 2015 Jul 26.