Effects Of Raloxifene On The Expression Of Transforming Growth Factor-beta1 Gene In Ovariectomized Rats Bone

Objective: Postmenopausal osteoporosis is associated with postmenopausal estrogen deficiency. Besides its bounding to estrogen receptor directly, estrogen affects the bone indirectly by regulating the production of cytokines. Among these cytokines, transforming growth factor- betal (TGF- β₁) plays an important role in the balance of bone resorption and bone formation. The effects of TGF-β₁ in bone repairing and bone remodling is gradually becoming the hot point. We used ovariectomized (OVX) female Wistar rats as animal osteoporosis models, and used semi-quantitative reverse transcriptase- polymerase chain reaction (RT-PCR) and histoimmunochemistry to detect the expression of TGF- β₁ , mRNA and protein in OVX rats bone, to study the significance of TGF- β₁ \ gene in the pathogenesis of PMO and the effects of Raloxifene on its expression. Methods: Fifty female virgin Wistar rats of three-point-five months old were randomly divided into five groups according to their body weight. There are ten rats in each group. Sham-operation group (S), OVX group (O), estrogen treated group (E), low-dose raloxifene treated group (RL), high-dose raloxifene treated group (RH), Sham-operation was performed in Sham group, bilateral ovariectomies were performed in the other groups. All rats were killed 12 weeks later.Bone mineral density (BMD) of lumbar vertebrae and femur was measured in vitro after sacrifice. We extracted total RNA directly from rat bone and detected the TGF- β₁ mRNA's expression by semi-quantitative reverse transcriptase-polymerase chain reaction (RT-PCR). TGF- β₁ protein levels was also detected byhistoimmunochemistry.Results: 1 - BMD of lumbar vertebra and whole femur was significantly increased in E, RL group (P<0.01). 2 ^ Morphological changes in rat tibia: Trabeculae of tibia were narrowed, broken scarce in OVX group, while the trabeculae in E, RL group were thickened,dense and unbroken. There was no broken trabeccula. , TGF - β₁ mRNA's expression of bone was significantly lower in OVX and RH group than that in S, E, RL group(P<0.05). The expression of bone TGF- β₁ protein was markedly higher in S group than that in O, RH group. Treatment with E and low-dose Raloxifene increased the expression of bone TGF-β₁ protein, which was similar to that of sham group.Conclusion: Raloxifene therapy on postmenopausal osteoporosis led to a significant enhancement in the expression of TGF- β₁ gene mRNA and protein. Estrogen also exhibited similar effects. It suggested a potential therapy of PMO with E and Raloxifene, which can increase the expression of TGF- β₁. TGF-β₁ might promote bone formation and inhibit bone resorption.