Regulation of Runx2 by post-translational modifications in osteoblast differentiation

Gomathi, K.; Akshaya, N.; Srinaath, N.; Moorthi, A.; Selvamurugan, N.

doi:10.1016/j.lfs.2020.117389

Cited by 107 publications

(68 citation statements)

References 98 publications

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“…Osteoporosis is a relatively prevalent disease that mainly leads to loss of bone mass and microstructural deterioration of bone tissues and eventually increases the susceptibility of patients to bone fractures [16,17]. It has been found that abnormal expression of many genes can cause osteoporosis, among which RUNX2 is the key transcription factor regulating osteoblast differentiation and bone formation during bone development [18,19]. RUNX2 is involved in the regulation of bone metabolism through a variety of pathways, but its specific mechanism is not clear [20].…”

Section: Discussionmentioning

confidence: 99%

MicroRNA-505 is involved in the regulation of osteogenic differentiation of MC3T3-E1 cells partially by targeting RUNX2

Chen

Cai

et al. 2020

J Orthop Surg Res

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Objective: Evidence suggests that microRNAs (miRNAs) regulate the expression of genes involved in bone metabolism. This study aimed to investigate the role of miR-505 in the osteogenic differentiation of MC3T3-E1 cells. Methods: We performed miRNA sequencing to identify differentially expressed miRNAs between MC3T3-E1 cells treated with osteogenic induction medium (OIM) and control cells. Bioinformatics analysis was performed by using the TargetScan and miRDB databases. The expression of miR-505 in MC3T3-E1 cells was detected during osteogenic differentiation. After transfection with miR-505 mimic or miR-505 inhibitor, MC3T3-E1 cells were induced to differentiate into osteoblasts, and the expression of osteogenic differentiation markers (Runt-related transcription factor 2 (RUNX2), alkaline phosphatase (ALP), osteopontin (OPN), osteocalcin (OCN), and osterix (OSX)) was detected. Results: miR-505 was the most downregulated miRNA among the differentially expressed miRNAs. The RUNX2 gene was identified as a potential target of miR-505 using the target prediction program. miR-505 expression was downregulated during osteogenic differentiation of MC3T3-E1 cells. The expression of osteogenic marker genes was inhibited in MC3T3-E1 cells after transfection with miR-505. However, the expression of osteogenic marker genes was upregulated after transfection with miR-505 inhibitor.Conclusion: This study is the first to report miR-505 could bind to the RUNX2 gene and thus regulate partly the dysfunction of osteoblasts differentiation, which is expected to be targets for the treatment of osteoporosis.

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Section: Discussionmentioning

confidence: 99%

MicroRNA-505 is involved in the regulation of osteogenic differentiation of MC3T3-E1 cells partially by targeting RUNX2

Chen

Cai

et al. 2020

J Orthop Surg Res

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“…et al, 2020). The activity and stability of RUNX2 are modulated at the post-transcription and post-translation levels by modifications such as phosphorylation, acetylation (Gomathi et al, 2020;Kim H.J. et al, 2020;Komori, 2020).…”

Section: Discussionmentioning

confidence: 99%

TRIM16 Promotes Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Modulating CHIP-Mediated Degradation of RUNX2

Zhao

Zhai

Liu

et al. 2021

Front. Cell Dev. Biol.

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Bone regeneration is the ultimate goal of periodontal therapies, in which osteogenic differentiation of human periodontal ligament stem cells plays a critical role. The tripartite motif (TRIM)16, an E3 ubiquitin ligase, is downregulated in periodontal tissues of patients with periodontitis, while the role of TRIM16 in the osteogenic differentiation of human periodontal ligament stem cells (hPDLSCs) is largely unknown. Firstly, we found that TRIM16 was increased throughout the osteogenic media induced differentiation of hPDLSCs. Then overexpression plasmids and specific short-hairpin RNAs (shRNAs) were constructed to manipulate the expression of target molecules. TRIM16 significantly promoted alkaline phosphatase activity, mineralized nodule formation, and positively regulated the expression of osteo-specific markers RUNX2, COL1A1 and OCN except the mRNA of RUNX2. Mechanistically, TRIM16 serves as a pivotal factor that stabilizes RUNX2 protein levels by decreasing CHIP-mediated K48-linked ubiquitination degradation of the RUNX2 protein. This study identified a novel mechanism of TRIM16 in regulating stability of the RUNX2 protein, which promoted the osteogenic differentiation of hPDLSCs. TRIM16 may be a potential target of stem cell based-bone regeneration for periodontal therapies.

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“…For example, miR-33-5p acts as a mechanosensitive microRNA that positively regulates osteoblastogenesis by repressing high mobility group AT-hook 2 (Hmga2), which is an inhibitor of osteoblastogenesis [20]. As a key transcription factor, Runt-related transcription factor 2 (Runx2) acts as a modulator regulating the differentiation of mesenchymal stem cells (MSCs) into osteoblasts, which further mature into osteocytes [21]. miRNA-194 promotes osteoblast differentiation by regulating Runx2 nuclear translocation mediated by signal transducer and activator of transcription (STAT1) [22].…”

Section: Mirna-mediated Mechanismsmentioning

confidence: 99%

The roles of miRNA, lncRNA and circRNA in the development of osteoporosis

et al. 2020

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Osteoporosis is a common metabolic bone disease, influenced by genetic and environmental factors, that increases bone fragility and fracture risk and, therefore, has a serious adverse effect on the quality of life of patients. However, epigenetic mechanisms involved in the development of osteoporosis remain unclear. There is accumulating evidence that epigenetic modifications may represent mechanisms underlying the links of genetic and environmental factors with increased risk of osteoporosis and bone fracture. Some RNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), have been shown to be epigenetic regulators with significant involvement in the control of gene expression, affecting multiple biological processes, including bone metabolism. This review summarizes the results of recent studies on the mechanisms of miRNA-, lncRNA-, and circRNA-mediated osteoporosis associated with osteoblasts and osteoclasts. Deeper insights into the roles of these three classes of RNA in osteoporosis could provide unique opportunities for developing novel diagnostic and therapeutic approaches to this disease.

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Regulation of Runx2 by post-translational modifications in osteoblast differentiation

Cited by 107 publications

References 98 publications

MicroRNA-505 is involved in the regulation of osteogenic differentiation of MC3T3-E1 cells partially by targeting RUNX2

MicroRNA-505 is involved in the regulation of osteogenic differentiation of MC3T3-E1 cells partially by targeting RUNX2

TRIM16 Promotes Osteogenic Differentiation of Human Periodontal Ligament Stem Cells by Modulating CHIP-Mediated Degradation of RUNX2

The roles of miRNA, lncRNA and circRNA in the development of osteoporosis

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