Effect of cyclooxygenase-2 on bone loss in ovariectomized rats

Abstract

To investigate mechanism of cyclooxygenase-2 (COX-2) in bone loss in a postmenopausal osteoporosis (PMOP) rat mode with ovarietomy (OVX). Forty female Sprague Dawley adult rats at age of 3 months were randomly divided into 4 groups, 10 in each group, including sham-operated (sham) group, OVX group, OVX treated with nilesteriol (OVX + E) group and OVX treated with aspirin (OVX + P) group. All rats in OVX, OVX + E and OVX + P groups underwent ovarietomy under abdominal anesthesia with 10% chloral hydrate. Rats in sham group were only taken with fat tissue with same weight under bilateral ovary. After surgery, penicillin was administered to prevent infection. At day 7 after surgery, agents were given by intragastric administration for 12 weeks. Nilestriol at 1.0 mg/kg was used in OVX + E group once a week, aspirin at 45 mg×kg⁻¹(×d⁻¹ was used in OVX + P group once a day. Saline with same volume was used in rats in sham and OVX groups. All agents were administered one time per day. Dose of agents were adjusted by weight per week. At end of study, bone mineral density (BMD) of right femurs and lumbar vertebrae 3-5 (L(3-5)) were measured. Morphology of bone was detected by hematoxylineosin, and expression of COX-2 was determined by immunohistochemistry staining. (1) BMD:BMD of right femur and L(3-5) was (0.209 ± 0.010) g/cm² and (0.230 ± 0.012) g/cm² in sham group and (0.181 ± 0.008) g/cm² and (0.201 ± 0.016) g/cm² in OVX group, which reached statistical difference (P < 0.01). BMD of right femur and L(3-5) was (0.203 ± 0.009) g/cm² and (0.224 ± 0.028) g/cm² in OVX + E group and (0.200 ± 0.011) g/cm² and (0.204 ± 0.003) g/cm² in OVX + P group, which were all higher than those in OVX group (P < 0.01, P < 0.05). However, there was no statistical difference in BMD between OVX + E and OVX + P group (P > 0.05). (2) Morphology of bone:bone trabeculae became fewer and degenerated in OVX group. However, bone trabeculae were regular and dense in OVX + P group and OVX + E group, which were similar to those in sham group. (3) Expression of COX-2:cells with COX-2 positive and expression of COX-2 around bone trabeculae in OVX group were more than those in sham, OVX + E and OVX + P group. COX-2 plays an important role in PMOP. Aspirin could prevent bone loss by decreasing COX-2 expression in OVX rats.