Nicotinamide Phosphoribosyltransferase Inhibitor APO866 Prevents IL-1β-Induced Human Nucleus Pulposus Cell Degeneration via Autophagy

摘要: Background/aims Intervertebral discs consist of an extracellular matrix (ECM) with a central gelatinous nucleus pulposus (NP) enclosed in outer layer known as the annulus fibrosus. ECM metabolic disorders result loss boundary between fibrosus and NP, which can lead to intervertebral disc degeneration (IDD). Proinflammatory cytokines, such interleukin (IL)-1β, mediate progression IDD. Nicotinamide phosphoribosyltransferase (Nampt) catalyzes first step biosynthesis nicotinamide adenine dinucleotide (NAD) is be induced by IL-1β. APO866 inhibitor NAD involved autophagy. LC3 (microtubule-associated protein 1 light chain 3) key regulator autophagy used indicator increased Herein, we investigate role regulating NP cells IL-1β mediated cell apoptosis. Methods were extracted from IDD tissues cultured DMEM/F12 medium. Nampt was different concentrations (0, 0.5, 1, 5, 10 ng/mL) for 24 h or treated ng/mL 0, 6, 12, 48 h. QRT-PCR western blots detect ECM-related expression tissue patients cells. Confocal analysis membrane-bound LC3, Aggrecan, Collagen II. Results expressed at higher levels severe grades (Grade IV V) compared low II III). In cells, h, degradative-associated proteins, ADAMTS4/5 MMP-3/13, decreased Aggrecan However, blocked induction, knockdown proteins that inhibited Moreover, evidence provided autophagic markers Beclin-1 indicated Furthermore, although downregulated IL-1β, this function inhibitor, 3-methyladenine. Conclusion protects induces inhibiting IL-1β-induced apoptosis, may have therapeutic potential