miR-19b-3p relieves intervertebral disc degeneration through modulating PTEN/PI3K/Akt/mTOR signaling pathway

Abstract

Emerging studies have revealed that non-coding RNAs contribute to regulating intervertebral disc degeneration (IVDD). Here, we intended to probe into the function of miR-19b-3p in IVDD evolvement. The miR-19b-3p level in the intervertebral disc (IVD) tissues of IVDD patients and IL-1β/TNF-α/hydrogen peroxide-treated human nucleus pulposus cells (HNPCs) was determined by quantitative real-time polymerase chain reaction (qRT-PCR). Also, qRT-PCR was conducted to examine the profiles of MMP-3, MMP-9, MMP-13, ADAMTS-4 and ADAMTS-5. The PTEN/PI3K/Akt/mTOR pathway was examined by Western blot (WB). The miR-19b-3p overexpression assay was carried out, and HNPC proliferation and apoptosis were compared by the cell counting kit-8 (CCK-8) assay and flow cytometry (FCM). In addition, the mechanism of action of miR-19b-3p was clarified using the PTEN inhibitor (VO-Ohpic triphosphate) or the mTOR inhibitor (Rapamycin) on the basis of IL-1β intervention and miR-19b-3p mimics transfection. Our results testified that miR-19b-3p expression was curbed in IVD tissues of the IVDD patients (vs. normal IVD tissues) and IL-1β-, TNF-α, or hydrogen peroxide-treated HNPCs. Up-regulating miR-19b-3p enhanced HNPC proliferation and hampered its apoptosis. Moreover, miR-19b-3p dampened the PTEN profile and activated the PI3K/Akt/mTOR pathway. Interestingly, attenuating PTEN reduced IL-1β-, TNF-α-, or hydrogen peroxide-mediated HNPC apoptosis and up-regulated PI3K/Akt/mTOR, while inhibiting the mTOR pathway offset the protective function of miR-19b-3p . Further mechanism studies illustrated that miR-19b-3p targeted the 3’untranslated region (UTR) of PTEN and abated the PTEN level. This research confirmed that miR-19b-3p suppressed HNPC apoptosis in the in-vitro model of IVDD by regulating PTEN/PI3K/Akt/mTOR pathway.

Emerging role and therapeutic implication of mTOR signalling in intervertebral disc degeneration

“…Recent studies have suggested that mTOR signalling is critical for maintaining IVD homeostasis. 24,25 Based on existing literature, we focused on the mTOR signalling pathway and its multiple biological functions in IVD cells to comprehensively clarify the role of the mTOR signalling pathway in IDD.…”

Nutritional deficiency induces nucleus pulposus cell apoptosis via the ATF4-PKM2-AKT signal axis

“…Previous studies indicated that activation of AKT signaling attenuated NPC apoptosis induced by high-magnitude compression or hyperosmotic conditions [ 49 ]. In addition, AKT could protect NPCs against apoptosis induced by some cytokines, such as IL-1β and TNF-α [ 50 ].…”

Scutellarin Protects Against Mitochondrial Reactive Oxygen Species-Dependent NLRP3 Inflammasome Activation to Attenuate Intervertebral Disc Degeneration

“…Previous studies have shown that TNF-α leads to disorganization of cell metabolism in IVD, including reduction of Col-2 as well as aggrecan, and elevation of MMPs and ADAMTSs, which contribute to the destruction of the ECM and pathogenesis of IVDD ( Liu Y. et al, 2021 ; Zhao and Li, 2021 ). TNF-α promotes the expression levels of catabolic markers, including MMP-13 and ADAMTS-5, which are harmful to ECM components during IVDD.…”