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

作　　者：Jing Feng Shuai Liu Sai Ma Jian Zhao Wei Zhang Wei Qi Pengchong Cao Zheng Wang Wei Lei 

机构地区：[1]Departrnent of Orthopedics, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China [2]Department of Cardiology, Xijing Hospital, Fourth Military Medical University, Xi'an 710032, China [3]Department of Orthoped-ics, China PLA General Hospital, Beijing 100853, China

出　　处：《Acta Biochimica et Biophysica Sinica》2014年第12期1024-1033,共10页生物化学与生物物理学报（英文版）

基　　金：This work was supported by a grant from the National Natural Science Foundation of China （No. 31170913）.

摘　　要：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 favor- able effect on osteoporosis and to explore the underlying mechanisms. Rat osteoporosis model （ovariectomy group, OVX） was established by bilateral ovariectomy. Three dif- ferent doses of resveratrol were used： 5 mg/kg/d （low- dosed, RESCD）, 25 mg/kg/d （medium-dosed, RESMD）, and 45 mg/kg/d （high-dosed, RESUD）. Results showed that RESLD did not show any significant effect on OVX altera- tions, while RESMD and RESXD significantly elevated the decreased bone mineral density induced by osteoporosis （RESMD 0.205±0.023, RESm） 0.214 ± 0.053 vs. OVX 0.165 ± 0.050 g/cm2 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 tomo- graphic results. In vitro results revealed that resveratrol promoted osteoblast differentiation of bone marrow mesen- chymal stromal cells, evidenced by the increase of ALP generation and mRNA expression of collagen 1 （P 〈 0.05; RESMD, RESm） vs. control group）. SIRT1 gene silencing by siRNA transfection blocked these beneficial effects of resveratrol （P〈0.05; RES ＋ SIRT1^KD vs RES^HD）. Western blot results showed that resveratrol activated SIRT1 and subsequently suppressed the activity of NF-κB with decreased expression level of p-IκBa and NF-κB p65 （P〈 0.05）. Our findings verified the effects of specific dosed resveratrol on postmenopausal osteoporosis through osteoblast differentiation via SIRT1-NF-κB signaling pathway. This study suggested the therapeutic potential of resveratroi against osteoporosis and stressed the importance of effective doses.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 favor- able effect on osteoporosis and to explore the underlying mechanisms. Rat osteoporosis model （ovariectomy group, OVX） was established by bilateral ovariectomy. Three dif- ferent doses of resveratrol were used： 5 mg/kg/d （low- dosed, RESCD）, 25 mg/kg/d （medium-dosed, RESMD）, and 45 mg/kg/d （high-dosed, RESUD）. Results showed that RESLD did not show any significant effect on OVX altera- tions, while RESMD and RESXD significantly elevated the decreased bone mineral density induced by osteoporosis （RESMD 0.205±0.023, RESm） 0.214 ± 0.053 vs. OVX 0.165 ± 0.050 g/cm2 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 tomo- graphic results. In vitro results revealed that resveratrol promoted osteoblast differentiation of bone marrow mesen- chymal stromal cells, evidenced by the increase of ALP generation and mRNA expression of collagen 1 （P 〈 0.05; RESMD, RESm） vs. control group）. SIRT1 gene silencing by siRNA transfection blocked these beneficial effects of resveratrol （P〈0.05; RES ＋ SIRT1^KD vs RES^HD）. Western blot results showed that resveratrol activated SIRT1 and subsequently suppressed the activity of NF-κB with decreased expression level of p-IκBa and NF-κB p65 （P〈 0.05）. Our findings verified the effects of specific dosed resveratrol on postmenopausal osteoporosis through osteoblast differentiation via SIRT1-NF-κB signaling pathway. This study suggested the therapeutic potential of resveratroi against osteoporosis and stressed the importance of effective doses.

关 键 词：resvemtrol OSTEOPOROSIS sirtuin 1 

分 类 号：Q257[生物学—细胞生物学] S858.317.1[农业科学—临床兽医学]