Long non‑coding RNA MALAT1 promotes high glucose‑induced rat cartilage endplate cell apoptosis via the p38/MAPK signalling pathway

Abstract

diabetes mellitus (dM) contributes to intervertebral disc degeneration (idd). The long non-coding rna MalaT1 has been revealed to play an important role in diabetes-associated complications. However, the specific role of MALAT1 in diabetes-associated idd has not been determined. The aim of the present study was to evaluate the roles of MALAT1 in the apoptosis of cartilage endplate (CEP) cells induced by high glucose and to explore the mechanisms underlying this effect. rat ceP cells were cultured in high-glucose medium (25 mM glucose) for 24 or 72 h. Cells cultured in medium containing 5 mM glucose were used as a control. Flow cytometry was used to detect the degree of apoptosis. Reverse transcription-quantitative PCR was used to measure the expression of MALAT1 mRNA. In addition, CEP cells were treated with different conditions (high glucose, high glucose + MalaT1 negative control, high glucose + MALAT1 RNAi, normal control) for 72 h. Flow cytometry was subsequently used to detect apoptosis and western blotting was used to measure the expression levels of total and phosphorylated p38. The results revealed that high glucose concentration promoted apoptosis and enhanced expression of MALAT1 in CEP cells. Furthermore, MALAT1 knockout decreased the expression levels of total and phosphorylated p38 and reduced the apoptosis of rat CEP cells. The results obtained in the present study indicated that MALAT1 may serve as an important therapeutic target for curing or delaying idd in patients with diabetes.

The Relationship between Diabetes Mellitus Type II and Intervertebral Disc Degeneration in Diabetic Rodent Models: A Systematic and Comprehensive Review

“…We identified 9511 published studies related to the issue IVDD. Out of these 27 manuscripts were related to the topic IVDD in diabetic rodent models, which is our research field of interest [ 3 , 15 , 43 , 47 , 52 , 53 , 54 , 55 , 56 , 57 , 58 , 59 , 60 , 61 , 62 , 63 , 64 , 65 , 66 , 67 , 68 , 69 , 70 ], see Table 4 and Table 5 . By further evaluation another four publications were excluded; two of them discussed the diabetic animal models used in IVDD, including rodents, but they were not related to IVDD.…”

“…Fourteen studies, investigated the overall pathogenesis of DM in the development of IVDD, see Table 4 , [ 53 , 54 , 55 , 56 , 57 , 59 , 61 , 63 , 64 , 65 , 67 , 69 ], while two studies investigated a specific pathogenesis element [ 58 , 66 ], such as the role of Sirt1/p53 axis in diabetic IVDD and the effect of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on apoptosis promoted by high glucose in rat cartilage endplate (CEP) cells. The other four studies (17.4%) investigated the effect and pathogenesis of risk factors [ 3 , 52 , 60 , 70 ], such as the degenerative effect on spine/IVD tissues induced by chronic ingestion of AGEs and the long exposure to high glucose concentrations.…”

“…A fewer number of studies combined both results from in vivo and in vitro experiments [ 58 , 63 ]. The in vitro studies allowed separate investigation of rodent IVD-derived cell types, such as AF [ 55 ], NP [ 65 ], notochordal cells [ 54 , 59 , 60 ], or even EP chondrocytes [ 66 , 67 ], in regard to the link between IVDD and T2DM. Strictly speaking, notochordal cells represent precursors of the NP cells characterized by a specific expression profile and associated with multipotent differentiation and self-renewal capacity and, hence, regenerative potential [ 5 ].…”

“…The studies related to notochordal cells included here did not further address this specific expression profile, and hence, their discrimination from NP cells remains elusive [ 54 , 59 , 60 ]. Looking at the in vitro studies when high glucose was used to mimic hyperglycemia conditions, the concentrations applied substantially differ (e.g., 25 mM [ 65 , 66 ]) versus 100, 200, or even 400 mM [ 54 , 55 , 56 , 59 , 60 ] or 5.5, 25, 50, 100, and 150 μM [ 58 ]. In this respect, one has to face the fact that the blood glucose levels in diabetic rats (ZDF rats, 4–8 weeks) or mice were between 20 and 30 mM [ 47 , 73 ].…”

Long noncoding RNA MIAT inhibits the progression of diabetic nephropathy and the activation of NF-κB pathway in high glucose-treated renal tubular epithelial cells by the miR-182-5p/GPRC5A axis

“…Mounting studies have suggested the correlations of lncRNAs with diabetic complications. For instance, MALAT1 enhanced the HG-induced cartilage endplate cell apoptosis by the p38/MAPK signaling pathway [ 30 ] and CASC15 promoted diabetes-induced chronic renal failure and podocyte apoptosis [ 31 ]. It has been found that MIAT facilitated diabetic retinopathy via activating TGF-β1 signaling [ 32 ] and induced cardiomyocyte apoptosis in diabetic cardiomyopathy by targeting the miR-22-3p/DAPK2 axis [ 33 ].…”