조골세포 세포사멸의 Estrogen 조절에 대한 Hsp27의 영향에 관한 연구 = HSP27 CONTRIBUTES TO ESTROGEN REGULATION OF OSTEOBLAST APOPTOSIS

다국어 초록 (Multilingual Abstract)

Estrogen may promote osteoblast/osteocyte viability by limiting apoptotic cell death. We hypothesize that hsp27 is an estrogen- regulated protein that can promote osteoblast viability by increasing osteoblast resistance to apoptosis. The purpose of this study was to determine the effect of estrogen treatment and heat shock on TNFα- induced apoptosis in the MC3T3-E1 cell line. Cells were treated with 0 - 100 nM 17βestradiol (or ICI 182780) for 0 - 24 hours before heat shock. After recovery, apoptosis was induced by treatment with 0 - 10 ng/ml TNFα. Hsp levels were evaluated by Northern and Western analysis using hsp27, hsp47, hsp70c and hsp70i - specific
reagents. Apoptosis was revealed by in situ labeling with Terminal Deoxyribonucleotide Transferase (TUNEL). A 5 - fold increase in hsp27 protein and mRNA was noted after 5 hours of treatment with 10 - 20 nM 17βestradiol prior to heat shock. Increased abundance of hsp47, hsp70c or hsp70i was not observed. TUNEL indicated that estrogen treatment also reduced (50%) MC3T3-E1 cell susceptibility to TNFα- induced apoptosis. Treatment with hsp27-specific antisense oligonucleotides prevented hsp27 protein expression and abolished the protective effects of heat shock and estrogen treatment on TNFα- induced apoptosis. Hsp27 is a determinant of osteoblast
apoptosis, and estrogen treatment increases hsp27 levels in cultured osteoblastic cells. Hsp27 contributes to the control of osteoblast apoptosis and may be manipulated by estrogenic or alternative pathways for the improvement of bone mass.