OVO homologue‐like 1 promotes osteoblast differentiation through BMP2 expression

Min, Hyeon-Young; Sung, Young Kwan; Kim, Eun-Jung; Jang, Won‐Gu

doi:10.1002/jcp.27821

Cited by 5 publications

(2 citation statements)

References 28 publications

(50 reference statements)

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“…BMP2 acts as a positive regulator of osteoblastic differentiation and promotes osteoblastic differentiation by activating the Smads signaling cascade [ 28 , 29 ]. RUNX2 expression is induced by BMP2 during osteogenic differentiation, and it can regulate the expression of osteogenic markers, such as osteocalcin (OCN), COL1A1, and osteopontin (OPN) [ 30 , 31 ]. Moreover, the high expression of BMP2 mitigates glucocorticoid-induced osteoporosis [ 32 ].…”

Section: Discussionmentioning

confidence: 99%

piRNA-36741 regulates BMP2-mediated osteoblast differentiation via METTL3 controlled m6A modification

Liu

Chen

et al. 2021

Aging

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The osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) is essential for bone formation, and its imbalance can lead to bone diseases such as osteoporosis. It is reported that PIWI-interacting RNA-36741 (piR-36741) is up-regulated during the osteogenic differentiation, but its role in regulating osteogenic differentiation remains unclear. Here, the primary human BMSCs were used to induce osteogenic differentiation, and the expression of piR-36741 and METTL3 (methyltransferase like 3) was up-regulated during the osteogenic differentiation of BMSCs. Moreover, interference with piR-36741 or METTL3 markedly hindered the osteogenic differentiation of BMSCs, which was manifested by a reduction in osteoblast marker expression (including RUNX2, COL1A1, OPN and OCN), osteogenic phenotype and matrix mineralization. Mechanistically, the piR-36741-PIWIL4 complex directly interacted with METTL3 and prevented METTL3-mediated m6A modification of BMP2 mRNA transcripts, thereby promoting BMP2 expression. And overexpression of BMP2 reversed the inhibitory effect of piR-36741 silence on osteogenic differentiation and the Smad pathway activity. In addition, administration with piR-36741 mimic alleviated ovariectomy-induced osteoporosis in mice. In conclusion, piRNA-36741 overexpression promoted osteogenic differentiation of BMSCs and mitigated ovariectomy-induced osteoporosis through METTL3-mediated m6A methylation of BMP2 transcripts.

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Section: Discussionmentioning

confidence: 99%

piRNA-36741 regulates BMP2-mediated osteoblast differentiation via METTL3 controlled m6A modification

Liu

Chen

et al. 2021

Aging

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“…Further research showed that the binding of FN and integrin α5 could induce the intramembrane osteogenesis. The upregulation of bone morphogenetic protein 2 (BMP2), a potent osteogenic inducer, and the upregulation of matrix Gla protein (MGP), a calcification inhibitor, are considered as the key of osteoblast differentiation [22][23][24][25]. Moreover, researchers found Runx2 is also necessary for the formation of bone tissue, and it is considered to be the most important transcription factor for osteoblast differentiation and the key to osteoblast differentiation [26].…”

Section: Introductionmentioning

confidence: 99%

Fibronectin/α5 Integrin Contribute to Hypertension-Associated Arterial Ageing and Calcification through Affecting BMP2/MGP Imbalance and Enhancing Vascular Smooth Muscle Cell Phenotypic Transformation

Shi,

Zhang,

et al. 2024

Gerontology

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Introduction: Hypertension can accelerate and aggravate the process of arterial ageing and calcification. However, the mechanism behind has yet to be well elucidated. Methods: Here, we monitored the dynamic changes of fibronectin (FN)/α5 integrin, bone morphogenetic protein 2/matrix Gla protein (BMP2/MGP) and Runx2 in the aorta of spontaneously hypertensive rats (SHR) and thoracic aortic vascular smooth muscle cells (VSMCs), also the phenotypic transformation of VSMCs during the process of arterial ageing and calcification. Further, study on arterial ageing and calcification through antagonist experiments at the molecular level was explored. Results: We found extracellular FN and its α5 integrin receptor expressions were positively associated with arterial ageing and calcification in SHR during ageing, as well in VSMCs from SHR in vitro. Integrin receptor inhibitor of GRGDSP would delay this arterial ageing and calcification process. Moreover, the elevated FN and α5 integrin receptor expression evoked the disequilibrium of BMP2/MGP, where the expression of BMP2, a potent osteogenic inducer, increased while MGP, a calcification inhibitor, decreased. Furthermore, it was followed by the upregulation of Runx2 and the phenotypic transformation of VSMCs from the contractile phenotype into the osteoblast-like cells. Notably, BMP2 antagonist of rm Noggin was sufficient to ameliorate the ageing and calcification process of VSMCs and exogenous BMP2 adding accelerate and aggregate the process. Conclusion: Our study revealed that hypertension-associated arterial ageing and calcification might be a consequence that hypertension up-regulated FN and its high binding affinity integrin α5 receptor in the aortic wall, which in turn aggravated the imbalance of BMP2/MGP, promoted the transcription of Runx2, and induced the phenotypic transformation of VSMCs from the contractile phenotype into the osteoblast-like cells. Our study would provide insights into hypertension-associated arterial ageing and calcification and shed new light on the control of arterial calcification, especially for those with hypertension.

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The role of zinc finger proteins in the fate determination of mesenchymal stem cells during osteogenic and adipogenic differentiation

Li,

Liu,

et al. 2024

The International Journal of Biochemistry & Cell Biology

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OVO homologue‐like 1 promotes osteoblast differentiation through BMP2 expression

Cited by 5 publications

References 28 publications

piRNA-36741 regulates BMP2-mediated osteoblast differentiation via METTL3 controlled m6A modification

piRNA-36741 regulates BMP2-mediated osteoblast differentiation via METTL3 controlled m6A modification

Fibronectin/α5 Integrin Contribute to Hypertension-Associated Arterial Ageing and Calcification through Affecting BMP2/MGP Imbalance and Enhancing Vascular Smooth Muscle Cell Phenotypic Transformation

The role of zinc finger proteins in the fate determination of mesenchymal stem cells during osteogenic and adipogenic differentiation

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