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.

Long‐term testosterone depletion attenuates inflammatory bone resorption in the ligature‐induced periodontal disease model

“…In fact, the aromatization rate of exogenously‐administered testosterone is higher than that of the naturally‐produced testosterone . Of note, the bone‐sparing effects of estrogens are long acknowledged; and the estrogen‐induced attenuation of experimental osteoporis in female ovariectomized rats is mediated, at least in part, by the inhibition of IL‐6 and IL‐1 production . Interestingly there is evidence that even immune cells, such as macrophages, when present in non‐inflamed microenvironments have a less pronounced conversion of testosterone into estradiol .…”

“…37,38 Of note, the bone-sparing effects of estrogens are long acknowledged; 39 and the estrogen-induced attenuation of experimental osteoporis in female ovariectomized rats is mediated, at least in part, by the inhibition of IL-6 and IL-1 production. 40 Interestingly there is evidence that even immune cells, such as macrophages, when present in non-inflamed microenvironments have a less pronounced conversion of testosterone into estradiol. 41 This phenomenon may be related with distinct biological mechanisms for the indirect effects of testosterone on cytokine production in noninflamed and inflamed gingival tissue.…”

Estradiol and zinc-doped nano hydroxyapatite as therapeutic agents in the prevention of osteoporosis; oxidative stress status, inflammation, bone turnover, bone mineral density, and histological alterations in ovariectomized rats

“…Based on the evidence of effectiveness, cost, and safety, standard HRT should be considered one of the first-line therapies for the prevention and treatment of fractures in postmenopausal women younger than 60 years ( Cobin et al, 2017 ; Levin et al, 2018 ). Hormone replacement therapy (HRT) in the form of either combined estrogen and progesterone or estrogen alone is effective in reducing the number of both vertebral and non-vertebral fractures in postmenopausal women ( Jin et al, 2017 ). Thus, standard HRT is effective in preventing bone loss associated with menopause and decreases the incidence of all osteoporosis-related fractures, including vertebral and hip fractures ( De Villiers and Stevenson, 2012 ).…”

Integration of Proteomics and Metabonomics in Exploring the Protecting Mechanism of Gushukang Capsule in Osteoporosis Rats

“…Recent research highlights the potential role of PUFA in the in ammatory regulation of bone remodeling via several cellular pathways [36][37][38]. The combined use of n-3 PUFA and E2 exerted synergistic bone-protective e cacy through upregulation of RUNX2, an essential transcription factor for bone formation, as well as the suppression of bone-resorbing cytokine IL-1β [39].…”