title: 17β-estradiol protects against apoptosis induced by interleukin-1β in rat nucleus pulposus cells by down-regulating MMP-3 and MMP-13.
abstract: In our previous study, 17β-estradiol was proved to protect rat annulus fibrosus cells against apoptosis induced by interleukin-1β (IL-1β). However, whether 17β-estradiol has protective effect on rat nucleus pulposus cells remains unclear. The purpose of this study was to further explore the effects of 17β-estradiol on rat nucleus pulposus cells based on IL-1β-induced apoptosis. TUNEL assay and Annexin V/PI double staining were used to detect apoptosis and revealed that IL-1β induced notable apoptosis, which was reversed by 17β-estradiol. Meanwhile, cell viability and binding ability were decreased by IL-1β, but activated caspase-3 was increased. However, all of the detected effects of IL-1β were eliminated by 17β-estradiol. Furthermore, real-time quantitative RT-PCR was used to further find that IL-1β downregulated expression level of type II collagen, aggrecan, tissue inhibitor of matrix metalloproteinase (TIMP)-1, while upregulated matrix metalloproteinase (MMP)-3, MMP-13 and Bcl-2, which was further confirmed by western blot. Finally, 17β-estradiol was proved to abolish the above negative effects of IL-1β. In summary, this work presented that IL-1β maybe induced apoptosis of rat nucleus pulposus cells, which was resisted by 17β-estradiol by down-regulating MMP-3 and MMP-13 via a mitochondrial pathway. This research provides a novel insight into the anti-apoptotic effect of 17β-estradiol on IL-1β-induced cytotoxicity, and may potentially lead to a better understanding of the clinical effects of 17β-estradiol, especially in terms of intervertebral disc degeneration.
authors.affiliation: Department of Spinal Surgery, The Third Hospital of Hebei Medical University, 139 Ziqiang Road, Shijiazhuang, 050051, China.
authors.forename: Si-Dong
authors.initials: SD
authors.lastname: Yang
authors.forename: Da-Long
authors.initials: DL
authors.lastname: Yang
authors.forename: Ya-Peng
authors.initials: YP
authors.lastname: Sun
authors.forename: Bao-Lin
authors.initials: BL
authors.lastname: Wang
authors.forename: Lei
authors.initials: L
authors.lastname: Ma
authors.forename: Shi-Qing
authors.initials: SQ
authors.lastname: Feng
authors.forename: Wen-Yuan
authors.initials: WY
authors.lastname: Ding
mesh_terms: D053674:Aggrecans / Q000235:genetics / Q000378:metabolism; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D024043:Collagen Type II / Q000235:genetics / Q000378:metabolism; D004958:Estradiol / Q000494:pharmacology*; D005786:Gene Expression Regulation; D053583:Interleukin-1beta / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D007403:Intervertebral Disc / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D008297:Male; D053509:Matrix Metalloproteinase 13 / Q000235:genetics* / Q000378:metabolism; D019278:Matrix Metalloproteinase 3 / Q000235:genetics* / Q000378:metabolism; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D061251:Primary Cell Culture; D020011:Protective Agents / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism
chemical_list: D053674:Aggrecans; D024043:Collagen Type II; D053583:Interleukin-1beta; D020011:Protective Agents; D019253:Proto-Oncogene Proteins c-bcl-2; C576839:TIMP1 protein, rat; D019715:Tissue Inhibitor of Metalloproteinase-1; D004958:Estradiol; D053148:Caspase 3; D053509:Matrix Metalloproteinase 13; D019278:Matrix Metalloproteinase 3