OBJECTIVE: The aim of this study was to explore whether long non-coding ribonucleic acid metastasis-associated lung adenocarcinoma transcript 1 (lncRNA MALAT1) could lead to osteoporosis (OP) by stimulating the activation of the mitogen-activated protein kinase (MAPK) signaling pathway.
MATERIALS AND METHODS: The OP model was first successfully established in rats. The expression of lncRNA MALAT1 in OP rats and normal rats was detected via quantitative Polymerase Chain Reaction (qPCR). Bone marrow mesenchymal stem cells (BMSCs) were cultured and transfected to establish the MALAT1 knockdown model. Subsequently, the apoptosis of mesenchymal stem cells in MALAT1 siRNA group and NC siRNA group was detected via flow cytometry. Meanwhile, the expressions of the MAPK signaling pathway proteins related to OP were detected via Western blotting. After alkaline phosphatase (ALP) staining in cells of both groups, early osteogenic differentiation of BMSCs was observed.
RESULTS: The results of qPCR showed that the expression of lncRNA MALAT1 in OP rats was significantly lower than that of normal rats. It was observed under a fluorescence microscope that there were a large number of siRNA particles in BMSCs. The expression of lncRNA MALAT1 in cells was detected via Real Time-fluorescence qPCR as well. The results indicated that siRNA transfection could effectively inhibit the expression of lncRNA MALAT1, indicating successful transfection. Flow cytometry revealed that no significant difference was observed in the apoptosis of BMSCs between the MALAT1 siRNA group and NC siRNA group. Besides, the results of Western blotting showed that the expression levels of the MAPK signaling pathway-related proteins extracellular signal-regulated kinase 1/2 (ERK1/2) and P38 in MALAT1 siRNA group were significantly higher than those of the NC siRNA group. This indicated that inhibiting the expression of lncRNA MALAT1 might promote the activation of the OP-related MAPK pathway. According to the results of ALP staining, the depth of staining in MALAT1 siRNA group was markedly declined when compared with the NC siRNA group. Quantification of ALP activity demonstrated that ALP activity in the MALAT1 siRNA group was markedly declined compared with the NC siRNA group. The above results suggested that suppressing the expression of lncRNA MALAT1 could reduce the ALP activity of BMSCs. Furthermore, lncRNA MALAT1 inhibited osteogenic differentiation of BMSCs.
CONCLUSIONS: LncRNA MALAT1 was lowly expressed in OP rats. Moreover, it inhibited osteogenic differentiation of BMSCs by enhancing the activation of the MAPK signaling pathway, thereby promoting OP progression.Free PDF Download
To cite this article
S. Zheng, Y.-B. Wang, Y.-L. Yang, B.-P. Chen, C.-X. Wang, R.-H. Li, D. Huang
LncRNA MALAT1 inhibits osteogenic differentiation of mesenchymal stem cells in osteoporosis rats through MAPK signaling pathway
Eur Rev Med Pharmacol Sci
Vol. 23 - N. 11