miR‐145 suppresses osteogenic differentiation by targeting Sp7

Despite extensive research on osteoblast differentiation and proliferation in mesenchymal stem cells (MSCs), the accurate mechanism remains to be further elucidated. MicroRNAs have been reported to be key regulators of osteoblast differentiation and proliferation. Here, we found that miR‐144‐3p is down‐regulated during osteoblast differentiation of C3H10T1/2 cells. Overexpression of miR‐144‐3p inhibited osteogenic differentiation, whereas inhibition of miR‐144‐3p reversed this process. Furthermore, miR‐144‐3p inhibited the proliferation of C3H10T1/2 cells by arresting cells at the G0/G1 phase. Results from bioinformatics analysis, luciferase assay and western blotting demonstrated that miR‐144‐3p directly targeted Smad4. Additionally, Smad4 knockdown blocks the effects of miR‐144‐3p inhibitor. Therefore, we conclude that miR‐144‐3p negatively regulates osteogenic differentiation and proliferation of C3H10T1/2 cells by targeting Smad4.

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“…Recently, a growing body of evidence has revealed that miRNAs play essential roles in osteoblast differentiation [22][23][24][25].…”

Section: Discussionmentioning

confidence: 99%

MiR‐144‐3p regulates osteogenic differentiation and proliferation of murine mesenchymal stem cells by specifically targeting Smad4

et al. 2016

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“…A number of miRNAs, including miR-30c, miR-133, miR-135a and miR-204 have been identified as regulating Runx2 expression during osteogenesis and pretreatment with these miRNAs results in a reduction of Runx2 protein and inhibits osteoblast differentiation [35, 36]. miR-145 also inhibits osteoblast differentiation by suppressing the expression of Osterix [37]. These miRNAs therefore may be targets for the regulation of osteoblast function.…”

Section: Osteoblastsmentioning

confidence: 99%

Mediators of inflammation and bone remodeling in rheumatic disease

Shaw

Gravallese

2016

Seminars in Cell & Developmental Biology

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Remodeling of bone is a continuous process that occurs throughout life. Under normal physiologic conditions, bone-resorbing osteoclasts and bone-forming osteoblasts are tightly coupled and regulated to ensure the proper balance, such that there is no net change in bone mass. However, inflammation perturbs normal bone homeostasis. The impact of inflammation on bone is dependent upon the anatomic site affected, cell types, factors and cytokines present in the local microenvironment, and local mechanical forces. Cytokines are central to the pathogenesis of inflammation-induced bone loss and contribute to the uncoupling of osteoclast-mediated bone resorption and osteoblast-mediated bone formation, thereby disrupting normal remodeling. In this review, we will discuss the effects of cytokines on bone in two settings, rheumatoid arthritis (RA) and spondyloarthritis (SpA), a disease category that includes ankylosing spondylitis (AS), psoriatic arthritis (PsA), reactive arthritis, inflammatory bowel disease, and juvenile onset spondyloarthropathy. The outcome for bone in these disease settings is quite different, and an understanding of the pathogenic mechanisms leading to the net impact on bone has been essential in developing new therapeutic approaches to bone health in these diseases.

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“…It was recently revealed that miRNAs have been involved in mediating the osteogenic differentiation of osteoblasts and mesenchymal stem cells (MSCs). MiR-143 and miR-145 were decreased in osteogenic differentiation, and their overexpression suppressed osteogenic differentiation by targeting Osterix and Sp7 transcription factor 7 (Sp7) in vitro, respectively [12,13]. MiR-155 is induced by Interferon-β and inhibits osteoclast differentiation by targeting suppressor of cytokine signaling 1 (Socs1) and microphthalmia-associated transcription factor (Mitf), two essential regulators of osteoclastogenesis [14].…”

Section: Introductionmentioning

confidence: 99%

Hypoxia-Induced MicroRNA-429 Promotes Differentiation of MC3T3-E1 Osteoblastic Cells by Mediating ZFPM2 Expression

Huang

Peng

Cao

et al. 2016

Cell Physiol Biochem

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Background/Aims: Hypoxia has been reported to regulate osteoblastic differentiation of bone cells and cartilage development. However, information concerning the molecular mechanisms remains largely unknown. Methods: The expression of miR-429 was evaluated by quantitative real-time PCR analysis. To test whether miR-429 directly regulate the expression level of ZFPM2 at transcription level, dual-luciferase reporter gene assay was performed. Western blotting was performed to detect osteogenesis related protein expression. The cell proliferation, apoptosis, alkaline phosphatase activity and matrix mineralization were performed to assess the functions of miR-429 in vitro and in vivo the effects of miR-429 on fracture healing. Results: Expression of miR-429 was increased in MC3T3-E1 cells treated with 200 μM CoCl₂ by qRT-PCR, and overexpression of miR-429 promoted cell differentiation, and enhanced alkaline phosphatase activity and matrix mineralization. Luciferase reporter assays suggested that miR-429 directly targets the 3'UTR of ZFPM2. In addition, knockdown of ZFPM2 could phenocopy the effects of miR-429 expression. Furthermore, overexpression of ZFPM2 in miR-429-expressing MC3T3-E1 cells suppressed cell differentiation. Conclusions: Our results provide valuable insight into the potential role of hypoxia in regulation of osteoblastic cell differentiation.

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miR‐145 suppresses osteogenic differentiation by targeting Sp7

Cited by 85 publications

References 28 publications

MiR‐144‐3p regulates osteogenic differentiation and proliferation of murine mesenchymal stem cells by specifically targeting Smad4

MiR‐144‐3p regulates osteogenic differentiation and proliferation of murine mesenchymal stem cells by specifically targeting Smad4

Mediators of inflammation and bone remodeling in rheumatic disease

Hypoxia-Induced MicroRNA-429 Promotes Differentiation of MC3T3-E1 Osteoblastic Cells by Mediating ZFPM2 Expression

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