Protective effects of resveratrol on osteoporosis via activation of the SIRT1-NF-κB signaling pathway in rats

Abstract

The aim of the present study was to determine the protective effects of resveratrol on a rat model of osteoporosis and examine the associated mechanisms of its action. Rats were randomized into the following groups: Control, osteoporosis, osteoporosis + low-dose resveratrol, osteoporosis + middle-dose resveratrol and osteoporosis + high-dose resveratrol groups. Resveratrol treatment was administered 7 days after surgery for 8 weeks. ELISA assay was used to analyze alkaline phosphatase (ALP) and osteocalcin (OC) protein levels. Western blotting was performed to assess the protein expression of sirtuin 1 (SIRT1), nuclear factor (NF)-κB and NF-κB inhibitor (IkB) α. In the present study, the results indicated that resveratrol markedly improved the bone mineral density value, femoral porosity and bone mechanical tests in osteoporosis rats. Administration of resveratrol significantly decreased the serum levels of ALP and OC in rats with osteoporosis. Finally, treatment with resveratrol significantly promoted the protein expression of SIRT1, suppressed NF-κB and activated the IkBα protein expression in rats with osteoporosis. In conclusion, treatment with resveratrol significantly improved the final body weight of the osteoporosis rats via the SIRT1-NF-κB signaling pathway. The present study suggested that resveratrol exerted a protective effect on osteoporosis through activation of the SIRT1-NF-κB signaling pathway in rats.

Keywords: nuclear factor-κB; osteoporosis; resveratrol; sirtuin 1.

Figure 1.

Chemical structure of resveratrol.

Figure 2.

Final body weight of rats in the various experimental groups. The weight was comparable among the groups with no significant differences. Ost, osteoporosis; RES, resveratrol; LD, low-dose; MD, middle-dose; HD, high-dose.

Figure 3.

Histological images showing the bone mineral density in each experimental group, obtained following hematoxylin and eosin staining. Magnification, ×40. Ost, osteoporosis; RES, resveratrol; LD, low-dose; MD, middle-dose; HD, high-dose.

Figure 4.

BMD values in the experimental group, showing increased BMD in the RES (MD) and RES (HD) groups. *P<0.01 vs. control group; ^#P<0.01 vs. Ost group. BMD, bone mineral density; Ost, osteoporosis; RES, resveratrol; LD, low-dose; MD, middle-dose; HD, high-dose.

Figure 5.

Serum levels of (A) ALP and (B) OC in osteoporosis rats, as determined by ELISA. *P<0.01 vs. control group; ^#P<0.01 vs. Ost group. ALP, alkaline phosphatase; OC, osteocalcin; Ost, osteoporosis; RES, resveratrol; LD, low-dose; MD, middle-dose; HD, high-dose.

Figure 6.

Femoral porosity based on the pixel intensity of (A) proximal, (B) mid-shaft and (C) proximal epiphysis in osteoporosis rats. *P<0.01 vs. control group; ^#P<0.01 vs. Ost group. Ost, osteoporosis; RES, resveratrol; LD, low-dose; MD, middle-dose; HD, high-dose.

Figure 7.

Bone mechanical tests, showing the percentages of (A) peak load and (B) ultimate stiffness of the femur in osteoporosis rats. *P<0.01 vs. control group; ^#P<0.01 vs. Ost group. Ost, osteoporosis; RES, resveratrol; LD, low-dose; MD, middle-dose; HD, high-dose.

Figure 8.

SIRT1 protein expression, determined by western blot analysis. (A) The western blots and (B) the quantified results of SIRT1 protein expression are shown. ^#P<0.01 vs. Ost group. SIRT1, sirtuin 1; Ost, osteoporosis; RES, resveratrol; LD, low-dose; MD, middle-dose; HD, high-dose.

Figure 9.

Western blot analysis of NF-κB protein expression as shown in the (A) western blots and (B) quantified levels. ^#P<0.01 vs. Ost group. Ost, osteoporosis; RES, resveratrol; LD, low-dose; MD, middle-dose; HD, high-dose.

Figure 10.

Western blot analysis of IkBα protein expression as shown in the (A) western blots and (B) quantified levels. ^#P<0.01 vs. Ost group. Ost, osteoporosis; RES, resveratrol; LD, low-dose; MD, middle-dose; HD, high-dose.