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雌激素通过调节细胞因子治疗骨质疏松症的机理

Mechanism of Treatment of Osteoporosis by Estrogen in Modulating Cytokine

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【作者】 崔竹梅王言奎戴淑真陈竹香

【Author】 Cui Zhumei,et al

【机构】 青岛医学院附属医院

【摘要】 绝经后骨质疏松(postmenopausalosteoporosis)是由于手术或自然绝经后雌激素低落引起的骨质疏松。在绝经后最初5~10年内雌激素的缺乏而引起骨吸收增加导致骨量丢失增多是主要的病理因素,其特征是全身的骨量减少及骨组织微结构改变致骨...

【Abstract】 Postmenopausal osteoporosis is a heterogeneous disorder begins after natural or surgical menopause and leads to fracture within 15~20 years from cessation of the ovarian function.Estrogen depletion during menopause results in significant loss of calcium in the urine consistent with an imbalance remodeling sequence.The discovery of estrogen receptor in osteoblasts,their stromal precursors and osteoclasts suggests that a direct effect on bone or bone marrow cells may be involved.It can block osteoclasteogenesis.Estrogen can also have indirect effect on bone by modulating the production of one or more of cytokines.these cytokines have complex and overlapping effects on bone formation and resorption such as IL 1,TNF,M CSF,IL 6, IL 11 and TGF β.Several lines of evidence derived from in vivo animal models and human studies support a critical role for cytokine in regulation of postmenopausal bone loss.In postmenopausal women circulating monocytic production of IL 1 and TNF is elevated in comparison with premenopausal women.IL 1 and TNF markedly stimulate osteoclast formation by both stimulation of osteoclast and precursor proliferation.They also can increase the secretion of M CSF and IL 6,which can induce proliferation and differentiation of hemopoetic osteoclast precursors. Estrogen has been shown to decrease the steadystate expression of IL 1 and TNF mRNA in monocytes and then it can reduce the bone resorption.TGF b is a potent osteoblast mitogen.It can reduce the life span of osteoclasts through promoting apoptosis.Estrogen can increase the steady state level of TGF b mRNA and release of TGF b protein.So estrogen has a positive effect on bone formation. Cytokine inhibitors such as IL 1ra(IL 1 receptor antagonist) and TNFbp(TNF binding protein) have been isolated and sequenced.Rats treated with recombinant TNFbp and IL 1ra immediately after ovariectomey showed no bone loss,phenomenon identical to what is observed after ovariectomy in rats administered estrogen.The cytokine inhibitors may be used in the treatment of postmenopausal osteoporosis in future.

  • 【文献出处】 基础医学与临床 ,BASIC MEDICAL SCIENCES AND CLINICS , 编辑部邮箱 ,1998年03期
  • 【分类号】R965
  • 【被引频次】3
  • 【下载频次】65
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