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.

Insulin-Like Growth Factor 1 Activates PI3k/Akt Signaling to Antagonize Lumbar Disc Degeneration

“…Although the molecular basis underlying the development of LDD has been extensively studied [26,27], a role of matrix metalloproteinase 3 (MMP3) in the disease initiation and progression has only been recently reported [5][6][7][8][9][10][11]. Nevertheless, the exact molecular mechanisms by which MMP3 regulates LDD have not been clarified.…”

“…Especially, a role of matrix metalloproteinase 3 (MMP3) in the disease initiation and progression has been recently acknowledged [5][6][7][8][9][10][11][12]. However, the exact molecular regulation of MMP3 in the LDD setting remains largely unknown.…”

Autophagy: A double-edged sword in intervertebral disk degeneration

“…Although IVD cell loss due to apoptosis continues to occur throughout life, excessive apoptosis of IVD cell has been considered as an important cause of disc degeneration [94][95][96][97]. As mentioned above, autophagy is a caspase-independent type II programmed cell death, but a close link exists between autophagy and apoptosis [98,99].…”

17β-Estradiol Inhibites Tumor Necrosis Factor-α Induced Apoptosis of Human Nucleus Pulposus Cells via the PI3K/Akt Pathway

“…Previous articles showed that numerous factors could cause the aberrant apoptosis of NPCs [29,30], including cytotoxic [31], chronic unpredictable stress [32], mechanical loading, altered biomechanics, and extracellular matrix degradation [33] all which induced apoptosis of IVD cells in vivo or in vitro . Both Yang et al [34] and Wei et al [35] found that IL-1β could induce rat apoptosis of NPCs. TNF-α is one type of inflammatory cytokines which is secreted by monocytes and macrophages, and plays an important role in inflammatory response, cells proliferation, and apoptosis [36,37].…”

“…Activated p-Akt promotes cell proliferation and inhibits cell apoptosis by regulating downstream proteins including BAD, GSK-3β, and NF-κB [48]. In our previous studies [23,24,34], 17β-E2 was found to have a protective effect on rat NPCs via the upregulation of type II collagen (COL2a1) and aggrecan, and downregulation of MMP-3 and MMP-13 [49]. In the present study, we further confirmed the effect of 17β-E2 against TNF-α induced apoptosis for human NPCs.…”