lncRNA MALAT1 promotes osteogenic differentiation through the miR‐217/AKT3 axis: A possible strategy to alleviate osteoporosis

Abstract

Background: Accumulating evidence demonstrates that long non-coding RNAs (lncRNAs) are associated with the development of osteoporosis. The present study aimed to investigate the effect of metastasis-associated lung adenocarcinoma transcript 1 (MALAT1) on osteogenic differentiation in osteoporosis.Methods: MALAT1 levels were detected by a real-time polymerase chain reaction (RT-qPCR). Moreover, the levels of osteogenic differentiation-related factors (Bmp4, Col1a1 and Spp1) were measured by a RT-qPCR and western blotting. Alkaline phosphatase (ALP) activity was detected using an ALP staining assay.Results: MALAT1 levels were downregulated in hindlimb unloading mice and simulated in microgravity (MG) treated MC3T3-E1 cells. Moreover, MG treatment induced the downregulation of the expression of ALP, BMP4, Col1a1 and Spp1, whereas overexpression of MALAT1 abolished the downregulation. MG also inhibited ALP activity, whereas MALAT1 reversed the effect. Furthermore, miR-217 was identified as a target of MALAT1, and AKT3 was verified as a target of miR-217.Overexpression of miR-217 rescued the promotion of osteogenic differentiation induced by MALAT1 in MG treated cells. Knockdown of AKT3 abolished the facilitation of osteogenic differentiation induced by downregulation of miR-217.Conclusions: MALAT1 promotes osteogenic differentiation through regulating miR-217/AKT3 axis, suggesting that MALAT1 is a potential target with respect to alleviating osteoporosis.

GATA4-activated lncRNA MALAT1 promotes osteogenic differentiation through inhibiting NEDD4-mediated RUNX1 degradation

“…MALAT1 was found to be downregulated in patients with PMOP, and MALAT1 levels were negatively associated with severity of PMOP [ 33 ]. Song et al suggested that MALAT1 expression was suppressed in hindlimb unloading mice and simulated microgravity treated cells, and overexpression of MALAT1 alleviated osteoporosis through regulating miR-217/AKT3 axis [ 34 ]. Furthermore, the role of MALAT1 in promoting osteogenic differentiation has been reported in a variety of cells, such as human periodontal ligament stem cells [ 35 ], renal interstitial fibroblasts [ 36 ], and BMSCs [ 7 ].…”

Bioinformatics analysis identification of AKT3 and RAC1 as key genes in postmenopausal osteoporosis

“…These hub genes are primarily involved in the processes of cell proliferation and differentiation (24)(25)(26)(27)(28)(29)(30)(31). Some genes are also reported to be involved in the formation of osteoclasts (32,33).…”

The regulatory activities of MALAT1 in the development of bone and cartilage diseases

“…Furthermore, the lncRNAs-transcription factor (TF) feedback loops are identified. Specifically, lncRNAs and TFs may compose feedback loops to mediate osteoblast differentiation, due to that TFs can directly mediate the differentiation activity by binding to the DNA-regulatory elements of lncRNAs (37).…”

“…MALAT1 has been considered as a biomarker in OP and is related to osteogenic differentiation ( 38 ). During the culture period of human MSCs, the osteogenic differentiation is developed from day 1 to 14.…”

“…In human aortic valve interstitial cells (hAVICs), MALAT1 functions as a positive mediator in osteogenic differentiation through Smad4 by suppressing the expression of miR-204 ( Table 1 ), as indicated by increased expression of ALP and osteocalcin (OCN) and mineralization ( 44 ). Overexpression of MALAT1 can promote osteogenic differentiation by regulating the activity of miR-127/AKT3 axis, alleviating OP ( 38 ). Consistently, the expression of MALAT1 is up regulated after osteogenic differentiation of BMSCs and down regulated after osteoclast differentiation of mononuclear macrophages.…”