lncRNA MALAT1 mediates osteogenic differentiation of bone mesenchymal stem cells by sponging miR-129-5p

Abstract

Background Bone mesenchymal stem cells (BMSCs) have good osteogenic differentiation potential and have become ideal seed cells in bone tissue engineering. However, the osteogenic differentiation ability of BMSCs gradually weakens with age, and the regulatory mechanism is unclear. Method We conducted a bioinformatics analysis, dual-luciferase reporter (DLR) experiment, and RNA binding protein immunoprecipitation (RIP) to explore the hub genes that may affect BMSC functions. Results The expression level of long non-coding RNA (lncRNA) metastasis-associated lung adenocarcinoma transcript 1 (Malat1) was significantly higher in the BMSCs from elderly than younger mice, while miR-129-5p showed the opposite trend. The results of alkaline phosphatase staining, quantitative reverse transcription PCR and western blot experiments indicated that inhibiting the expression of Malat1 inhibits the osteogenic differentiation of BMSCs. This effect can be reversed by reducing the expression of miR-129-5p. Additionally, DLR and RIP experiments confirmed that Malat1 acts as a sponge for miR-129-5p. Conclusion Overall, our study findings indicated that lncRNA Malat1 may play a critical role in maintaining the osteoblast differentiation potential of BMSCs by sponging miR-129-5p.

Long noncoding RNA MALAT1 inhibition attenuates sepsis‐induced acute lung injury through modulating the miR‐129‐5p/PAX6/ZEB2 axis

“…Such a regulatory mechanism exists in lncRNAs, miRNAs, and mRNAs, and regulates multiple biological processes, such as cell proliferation, migration, invasion, and apoptosis 46 . For instance, Yin et al 16 have indicated that MALAT1 functions as a sponge for miR‐129‐5p. MALAT1 downregulation inhibits SOX9 expression by binding to miR‐129‐5p, thereby suppressing the abnormal proliferation of small intestinal epithelial cells via the WNT/β‐catenin axis 47 .…”

“…It is identified and demonstrated that miR‐129‐5p can directly regulate MALAT1 and miR‐129‐5p mimics have the ability to restrain the development of colon cancer cells 15 . LncRNA MALAT1 might play an important role in sustaining the potential osteoblast differentiation of bone mesenchymal stem cells through sponging miR‐129‐5p 16 . In addition, MALAT1 could promote osteosarcoma cell development through the inhibition of miR‐129‐5p 17 .…”

“…15 LncRNA MALAT1 might play an important role in sustaining the potential osteoblast differentiation of bone mesenchymal stem cells through sponging miR-129-5p. 16 In addition, MALAT1 could promote osteosarcoma cell development through the inhibition of miR-129-5p. 17 Therefore, it is meaningful to probe the functions and underlying mechanisms of MALAT1 and its interaction with miR-129-5p in sepsisinduced ALI.…”

Long Non-Coding RNA Malat1 Increases the Rescuing Effect of Quercetin on TNFα-Impaired Bone Marrow Stem Cell Osteogenesis and Ovariectomy-Induced Osteoporosis

“…Several lncRNAs, including Malat1, H19, HOTAIR, MEG3 and DANCR, were largely involved in the osteoporosis. Malat1 and H19 could promote osteogenesis, while HOTAIR, MEG3 and DANCR inhibited osteogenesis in a Wnt/β-catenin-dependent manner [ 9 , 23 , 24 , 25 , 26 ]. Furthermore, MALAT1 repressed the LPS-induced inflammatory response by interacting with NF-κB [ 27 ].…”

Role of epigenetic regulatory mechanisms in age‐related bone homeostasis imbalance

“…GATA4 and MALAT1 expression was identified as downregulated in the bone tissue of 18‐month‐old mice through osteoporosis modeling. Moreover, in vitro tests revealed that MALAT1 binds to K‐homology splicing regulatory protein, which controls mRNA transcription, and decreases the expression of ubiquitination‐activating enzyme 98 . By reducing ubiquitination‐activating enzyme expression, MALAT1 inhibits the degradation of downstream RUNX1 and encourages the formation of osteoblasts.…”