Dissertation

Effects of Resveratrol on the Expression of Critical Factors Involved in Bone Remodeling in Rat Osteoporosis Model

Khera, Alka

2010

Overview

Osteoporosis characterized by decrease in bone mass, is a major health problem affecting 2 in 3 women in postmenopausal years. Traditional therapies for post menopausal osteoporosis have emphasized the use of anti-resorption agents such as estrogen, calcitonin and bisphosphonates. Although these agents may prevent further bone loss in established osteoporosis, they cannot restore bone mass that has been lost already. Also some women are reluctant to take estrogen replacement therapy because of potentially increased cancer risks. Thus it is necessary to develop naturally occurring compounds or synthetic substances with less undesirable side effects that can substitute or reduce the need for drugs used currently.Resveratrol is a plant polyphenol that was shown to have beneficial effects of estrogen. While extensive data on mechanism of resveratrol’s protective effects against cardiovascular diseases and cancer is available its effect on bone metabolism is poorly understood. Thus it is important to study the effects of resveratrol on factors involved in bone remodeling and this will lead to the identification of molecular targets for designing of drugs that can be used to prevent osteoporosis. Resveratrol is considered to be a promising therapeutic for all the postmenopausal health problems. The molecular mechanism involved in osteoprotective effect of resveratrol has not even been interrogated. As such the number of studies that have reported the osteoprotective effect of resveratrol are scanty.So the present study was conducted to investigate the molecular mechanisms of protection conferred by resveratrol against estrogen deficiency induced osteoporosis, using surgical menopause model of rat. The study was conducted on three months old Sprague Dawley (SD) rats which were given resveratrol (0.7 and 5mg per Kg diet) for 1 month. The rats were randomly divided into six study groups each comprising 7 animals each, (i) sham operated control group(ii) ovariectomized (hi) ovariectomized treated with (β-estradiol (3.9mg/kg diet) (iv) sham operated treated with resveratrol (0.7mg/Kg diet) (v) ovariectomized treated with resveratrol (0.7 mg/Kg diet) (vi) ovariectomized treated with resveratrol (5 mg/Kg diet).At the end of 1 month , blood was collected to estimate serum osteoclastic and osteoblastic parameters. Femur was also removed and its proximal end was used to extract RNA and protein. Quantitative analysis of estrogen receptor α, β, vitamin D receptor (VDR), parathyroid hormone receptor was done at gene and protein levels in all the groups. Proinflammatory cytokines (IL-1β and TNF-α) were also checked in proximal end of the femur. Tibia was removed to analyze density, calcium, phosphorous and mineral content in the bone.Our study showed improvement in physiological and biochemical profile of ovariectomized animals when treated with resveratrol in dose dependent manner. Concomitant with the decrease in the levels of osteoporotic markers in resveratrol treated animals as compared to ovariectomized animals we observed an increase in the expression of ER-α, ER-β and VDR in resveratrol treated animals. The expression levels of PTHR which is an osteoclastic factor, decreased in experimental animals as compared to control animals. There was also decrease in cytokine levels when ovariectomized animals were treated with resveratrol.Hence our study can show that resveratrol has protective role in curing osteoporosis caused by estrogen deficiency by directly affecting the expression of critical factors involved in bone remodelling.

• Publisher: ProQuest Dissertations & Theses
• Subject: Obstetrics / Obstetrics and gynecology
• ISBN: 9798286485215