MicroRNA‐224 suppresses osteoblast differentiation by inhibiting SMAD4

Luo, Yuan; Cao, Xiaodong; Chen, Junfeng; Gu, Jian‐Wei; Zhao, Jitong; Sun, Junying

doi:10.1002/jcp.26596

Cited by 25 publications

(20 citation statements)

References 38 publications

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“…31 The Smad4 complex transcribes Runx2 and interacts with Runx2 to initiate the expression of other osteoblast genes. 32 Thus, Smad4 expression is mediated by Smad4/Runx2 signaling at the transcriptional level, and Smad4 regulates Runx2 activity and the expression of other osteoblast genes in a feedback loop. 33,34 The cytoskeleton has been shown to control the activation of Smad4/Runx2 signaling in mesenchymal cells upon external stimulation, and cell morphology remodeling and cytoskeletal organization can affect stem cell lineage commitment.…”

Section: Introductionmentioning

confidence: 99%

The Role of Tantalum Nanoparticles in Bone Regeneration Involves the BMP2/Smad4/Runx2 Signaling Pathway

Zhang¹,

Liu²,

Wang³

et al. 2020

IJN

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Background: In recent years, nanomaterials have been increasingly developed and applied in the field of bone tissue engineering. However, there are few studies on the induction of bone regeneration by tantalum nanoparticles (Ta NPs) and no reports on the effects of Ta NPs on the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) and the underlying mechanisms. The main purpose of this study was to investigate the effects of Ta NPs on bone regeneration and BMSC osteogenic differentiation and the underlying mechanisms. Materials and Methods: The effects of Ta NPs on bone regeneration were evaluated in an animal experiment, and the effects of Ta NPs on osteogenic differentiation of BMSCs and the underlying mechanisms were evaluated in cell experiments. In the animal experiment, hematoxylin-eosin (HE) staining and hard-tissue section analysis showed that Ta NPs promoted bone regeneration, and immunohistochemistry revealed elevated expression of BMP2 and Smad4 in cells cultured with Ta NPs. Results: The results of the cell experiments showed that Ta NPs promoted BMSC proliferation, alkaline phosphatase (ALP) activity, BMP2 secretion and extracellular matrix (ECM) mineralization, and the expression of related osteogenic genes and proteins (especially BMP2, Smad4 and Runx2) was upregulated under culture with Ta NPs. Smad4 expression, ALP activity, ECM mineralization, and osteogenesis-related gene and protein expression decreased after inhibiting Smad4. Conclusion: These data suggest that Ta NPs have an osteogenic effect and induce bone regeneration by activating the BMP2/Smad4/Runx2 signaling pathway, which in turn causes BMSCs to undergo osteogenic differentiation. This study provides insight into the molecular mechanisms underlying the effects of Ta NPs in bone regeneration.

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Section: Introductionmentioning

confidence: 99%

The Role of Tantalum Nanoparticles in Bone Regeneration Involves the BMP2/Smad4/Runx2 Signaling Pathway

Zhang¹,

Liu²,

Wang³

et al. 2020

IJN

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“…But another study in three types of cells (MC3T3-E1 cells, mouse and human BMSCs), miR-98-5p inhibited osteogenic differentiation by targeting HMGA2 (Zheng et al, 2019). And for miR-224, it inhibited osteoblast differentiation in mesenchymal stem cells by directly targeting Smad4 (Luo et al, 2018), but miR-224 regulated the expression of Rac1 to promoted osteogenic differentiation in human mesenchymal stem cells (Cai et al, 2019).…”

Section: Mirnas Regulate Other Factors In Osteoblastsmentioning

confidence: 97%

Roles of MicroRNAs in Bone Destruction of Rheumatoid Arthritis

Zhao

2020

Front. Cell Dev. Biol.

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As an important pathological result of rheumatoid arthritis (RA), bone destruction will lead to joint injury and dysfunction. The imbalance of bone metabolism caused by increased osteoclast activities and decreased osteoblast activities is the main cause of bone destruction in RA. MicroRNAs (MiRNAs) play an important role in regulating bone metabolic network. Recent studies have shown that miRNAs play indispensable roles in the occurrence and development of bone-related diseases including RA. In this paper, the role of miRNAs in regulating bone destruction of RA in recent years, especially the differentiation and activities of osteoclast and osteoblast, is reviewed. Our results will not only help provide ideas for further studies on miRNAs' roles in regulating bone destruction, but give candidate targets for miRNAs-based drugs research in bone destruction therapy of RA as well.

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“…Similarly, a previous study indicated that exposure to elevated phosphorus levels results in the upregulation of Runx2 expression and ALP activity ( 18 ). Runx2 is a notable transcription factor in the process of VSMC osteo-/chondrogenic transdifferentiation, which induces the expression of major bone matrix components, including type I collagen ( 5 ), osteocalcin ( 19 ) and OPN ( 20 ). Runx2 can be transcribed from the distal P1 promoter or the P2 promoter, resulting in the expression of two different subtypes (Runx2 I and II), which can be expressed in ossified and cartilage cells; both subtypes exhibit similar features in chondrocytes and osteoblasts.…”

Section: Discussionmentioning

confidence: 99%

microRNA‑103a regulates the calcification of vascular smooth muscle cells by targeting runt‑related transcription factor 2 in high phosphorus conditions

Bai

et al. 2021

Exp Ther Med

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Vascular calcification, such as atherosclerosis, is a serious complication of chronic kidney disease that is characterized by tunica media calcification, and has gained increasing attention from researchers. The commonly observed association between vascular calcification and osteoporosis suggests a link between bone and vascular disorders. As microRNAs (miRNAs) have a wide range of gene regulation functions, such as cell proliferation, apoptosis, stress and transdifferentiation, the current study aimed to determine whether miRNAs play a vital role in the calcification and osteoblastic differentiation of rat thoracic aorta vascular smooth muscle cells (VSMCs). Gene expression analysis was performed on seven miRNAs (miR-29a, -30b, -103a, -125b, -133a, -143 and -211) that maybe potentially involved in the differentiation of smooth muscle cells into osteoblastic cells. The results showed that the levels of miR-29a, -30b, -103a, -125b and -143 were markedly reduced in the VSMC calcification model, particularly miR-103a, whereas runt-related transcription factor 2 (RUNX2) expression was increased. Furthermore, it was found that the expression of RUNX2 was significantly decreased following the upregulation of miR-103a, and that the expression of RUNX2 was significantly increased by downregulating miR-103a in VSMCs. Therefore, it was concluded that miR-103a plays a notable role in the transdifferentiation of the VSMCs in high phosphorus-induced calcification by targeting the regulation of RUNX2, and may therefore constitute a new target for the diagnosis and treatment of vascular calcification.

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MicroRNA‐224 suppresses osteoblast differentiation by inhibiting SMAD4

Cited by 25 publications

References 38 publications

<p>The Role of Tantalum Nanoparticles in Bone Regeneration Involves the BMP2/Smad4/Runx2 Signaling Pathway</p>

<p>The Role of Tantalum Nanoparticles in Bone Regeneration Involves the BMP2/Smad4/Runx2 Signaling Pathway</p>

Roles of MicroRNAs in Bone Destruction of Rheumatoid Arthritis

microRNA‑103a regulates the calcification of vascular smooth muscle cells by targeting runt‑related transcription factor 2 in high phosphorus conditions

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