title: Synergistic attenuation of ovariectomy-induced bone loss by combined use of fish oil and 17β-oestradiol.
abstract: Oestrogen and n-3 PUFA, especially EPA and DHA, have been reported to have beneficial effects on bone loss. Thus, the purpose of the present study was to investigate the synergistic bone-protective mechanism of combined treatments of EPA+DHA supplementation and oestrogen injection in ovariectomised rats. Rats were fed a modified American Institute of Nutrition-93G diet with 0 %, 1 % or 2 % n-3 PUFA (EPA+DHA) relative to the total energy intake for 12 weeks. Rats were surgically ovariectomised at week 8, and after a 1-week recovery period rats were injected with either 17β-oestradiol-3-benzoate (E2) or maize oil for the last 3 weeks. Combined use of n-3 PUFA and E2 synergistically increased femoral cortical bone volume, bone mineral content and the bone expression of runt-related transcription factor 2 (RUNX2), but decreased the bone expression of IL-1β. Both n-3 PUFA and E2 decreased the bone expressions of IL-7, TNF-α and PPAR-γ, and increased the bone expression of oestrogen receptor-α. n-3 PUFA in the presence of E2 and E2 alone significantly decreased the bone expressions of IL-1β and IL-6 and increased the bone expression of RUNX2. E2 significantly decreased the serum levels of bone turnover markers and the bone expression of receptor activator of NF-κB ligand, but decreased the bone expression of osteoprotegerin. The combined use of n-3 PUFA and E2 exerted synergistic bone-protective efficacy through up-regulation of RUNX2, an essential transcription factor for bone formation, as well as the suppression of bone-resorbing cytokine IL-1β.
authors.affiliation: 1Department of Food and Nutrition,Hanyang University,222 Wangsimni-ro,Seongdong-gu,Seoul,04763,Republic of Korea.
authors.forename: Youri
authors.initials: Y
authors.lastname: Jin
authors.affiliation: 2Department of Food and Nutrition,Sungshin Women's University,55,Dobong-ro,76ga-gil,Gangbuk-gu,Seoul,01133,Republic of Korea.
authors.forename: Myoungsook
authors.initials: M
authors.lastname: Lee
authors.affiliation: 1Department of Food and Nutrition,Hanyang University,222 Wangsimni-ro,Seongdong-gu,Seoul,04763,Republic of Korea.
authors.forename: Yongsoon
authors.initials: Y
authors.lastname: Park
mesh_terms: D000818:Animals; D015519:Bone Density; D050071:Bone Density Conservation Agents / Q000494:pharmacology / Q000627:therapeutic use; D001851:Bone Diseases, Metabolic / Q000378:metabolism* / Q000517:prevention & control; D001862:Bone Resorption / Q000378:metabolism* / Q000517:prevention & control; D050659:Core Binding Factor Alpha 1 Subunit / Q000378:metabolism*; D004357:Drug Synergism; D004958:Estradiol / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000627:therapeutic use; D047628:Estrogen Receptor alpha / Q000378:metabolism; D005260:Female; D005269:Femur / Q000187:drug effects* / Q000378:metabolism; D005395:Fish Oils / Q000494:pharmacology* / Q000627:therapeutic use; D053583:Interleukin-1beta / Q000378:metabolism*; D015850:Interleukin-6 / Q000378:metabolism; D015851:Interleukin-7 / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D053244:Osteoprotegerin / Q000378:metabolism; D010052:Ovariectomy; D047495:PPAR gamma / Q000378:metabolism; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D050071:Bone Density Conservation Agents; D050659:Core Binding Factor Alpha 1 Subunit; D047628:Estrogen Receptor alpha; D005395:Fish Oils; D053583:Interleukin-1beta; D015850:Interleukin-6; D015851:Interleukin-7; D016328:NF-kappa B; D053244:Osteoprotegerin; D047495:PPAR gamma; C493717:Runx2 protein, rat; D014409:Tumor Necrosis Factor-alpha; C074283:estradiol 3-benzoate; D004958:Estradiol
keywords: 
                 n-3 PUFA;  BMC bone mineral content;  BV bone volume;  E2
                  17β-oestradiol-3-benzoate;  ER-α oestrogen receptor-α;  OPG osteoprotegerin;  OVX ovariectomised;  RANKL receptor activator of NF-κB ligand;  RUNX2 runt-related transcription factor 2; 17β-Oestradiol-3-benzoate; Bone loss; IL-1β
              ; Runt-related transcription factor 2