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Analysis of gene expression in human bone biopsies by polymerase chain reaction: Evidence for enhanced cytokine expression in postmenopausal osteoporosis

作者:Stuart H. Ralston · 发表于:Journal of Bone and Mineral Research · 年份:1994 · DOI:10.1002/jbmr.5650090614 · 被引用次数:177 · 研究领域:Bone Metabolism and Diseases、Bone health and osteoporosis research、Vitamin D Research Studies

Abstract It has been suggested that one of the mechanisms by which estrogen protects against postmenopausal osteoporosis is by modulating the production of cytokines, such as interleukin-1 (IL-1), tumor necrosis factors (TNF), and interleukin-6 (IL-6), in the bone microenvironment. In this study, reverse transcription/polymerase chain reaction (RT/PCR) was used to analyze expression of the mRNAs encoding these cytokines in freshly isolated human bone biopsy samples. Marked differences were found in the prevalence with which certain cytokines were expressed in different patient subgroups. Specifically, IL-1α, IL-1β, and IL-6 mRNAs were expressed significantly more often in bone samples from postmenopausal women with osteoporotic fractures than in postmenopausal women with normal bone density or postmenopausal women on hormone replacement therapy (HRT). The prevalence of IL-1α expression was 54% in bone samples from patients with osteoporotic fractures (n = 22), compared with 30% in nonosteoporotic postmenopausal patients (n = 10) and 10% in postmenopausal patients on HRT (difference between groups by χ test = 7.0; DF = 2,p < 0.05). Corresponding figures for IL-1β were 54 versus 30 versus 0% (χ = 8.6; DF = 2, p < 0.01) and, for IL-6, 94 versus 51 versus 40%; χ = 13.5; DF = 2, p < 0.01). TNF-α was expressed in a similar proportion of osteoporotic (63%) and normal postmenopausal patients (60%), whereas only 10% of HRT-treated patients showed expression of TNF-α (χ = 8.2; DF = 2, ...