Protective effects of resveratrol on postmenopausal osteoporosis: regulation of SIRT1-NF-κB signaling pathway

Postmenopausal osteoporosis severely jeopardizes human health. Seeking for therapeutic drugs without side effects is of great necessity. Our study was designed to investigate whether resveratrol, an agonist of SIRT1, could have favorable effect on osteoporosis and to explore the underlying mechanisms. Rat osteoporosis model (ovariectomy group, OVX) was established by bilateral ovariectomy. Three different doses of resveratrol were used: 5 mg/kg/d (lowdosed, RES LD ), 25 mg/kg/d (medium-dosed, RES MD ), and 45 mg/kg/d (high-dosed, RES HD ). Results showed that RES LD did not show any significant effect on OVX alterations, while RES MD and RES HD significantly elevated the decreased bone mineral density induced by osteoporosis (RES MD 0.205+0.023, RES HD 0.214+ + 0.053 vs. OVX 0.165+ 0.050, g/cm 2 respectively; P < 0.05). Serum markers alkaline phosphatase (ALP) and osteocalcin were moderately restored by resveratrol. Moreover, resveratrol improved bone structure in OVX rats, demonstrated by hematoxylin-eosin staining and micro-computed tomographic results. In vitro results revealed that resveratrol promoted osteoblast differentiation of bone marrow mesenchymal stromal cells, evidenced by the increase of ALP generation and mRNA expression of collagen 1 (P < 0.05; RES MD , RES HD vs. control group). SIRT1 gene silencing by siRNA transfection blocked these beneficial effects of resveratrol (P < 0.05; RES1 SIRT1 KD vs. RES HD ). Western blot results showed that resveratrol activated SIRT1 and subsequently suppressed the activity of NF-kB with decreased expression level of p-IkBa and NF-kB p65 (P < 0.05). Our findings verified the effects of specific dosed resveratrol on postmenopausal osteoporosis through osteoblast differentiation via SIRT1-NF-kB signaling pathway. This study suggested the therapeutic potential of resveratrol against osteoporosis and stressed the importance of effective doses.