雌激素对骨质疏松性骨折愈合过程BMP-4基因表达的影响

Effects of estrogens on BMP-4 gene expression during osteoporotic fracture healing

目的:研究雌激素对骨质疏松性骨折愈合骨形态发生蛋白-4(bonemorphogeneticprotein-4,BMP-4)基因定位分布的影响。方法:选用健康SD大鼠,随机分为卵巢切除(OVX)组、假手术对照(sham)组和雌激素替代治疗组(OVXE)。制成胫骨骨折愈合模型并分别于骨折后不同时点处死大鼠取材。通过光镜、电镜观察形态学和超微结构变化;采用原位杂交方法观察雌激素对BMP-4基因表达影响。结果:(1)OVX组在骨痂形态及成骨细胞和破骨细胞活性与OVXE组比较有明显差异,较sham组差异更大。(2)骨折后1-3dBMP-4mRNA表达强度:sham组<OVXE组<OVX组。结论:雌激素对胫骨骨折超微结构和BMP-4基因表达产生影响。雌激素对骨折愈合起重要调节作用。

AIM: To study the effects of estrogens on expression of BMP-4 in osteoporotic fracture healing, and the pathogenesis of improvement of osteoporotic fracture healing by estrogen. METHODS: 144 female SD rats were divided randomly into ovariectomy group (OVX), sham-operation group (sham) and estrogen replacement therapy group (OVXE). Closed fractures were produced manually in shaft of both tibias after intra-medullary fixation in all rats one month later. Calluses and soft tissue were collected at the date of 1st, 3rd, 5th, 7th, 14th, 28th, 56th, 112th day after fracture. The histological changes of calluses and the healing of trabecular bone with the structure changes of trabecular bone fiber were observed by microscope and activity of osteoblasts, osteoclasts by electron microscopy. The regularity of BMP-4 expression during osteoporotic fracture and the effect of estrogens on it were studied by in situ hybridization with BMP-4 cDNA probe. RESULTS: (1) Compared to OVXE group, the changes in callus density and arrange of trabecular bone, activity of osteoblasts and osteoclasts in OVX group were significantly different, and more remarkable changes were observed than that in sham group. (2) From 1 to 3 days after fracture, the signals of BMP-4 were positively detected and localized in the cells in parafractures hematoma and in the nearly appeared mesenchymal cells in the muscles adjacent to fracture site, and OVX>OVXE>sham (P<0.01). CONCLUSION: When estrogen deficient, bone turnover was enhanced with the increase in BMP-4 gene expression. Estrogens play an important role in fracture healing, estrogen replacement therapy may be effective.