The biological function of type I receptors of bone morphogenetic protein in bone

Su, Lin; Svoboda, Kathy K.H.; Feng, Jian Q.; Jiang, Xinquan

doi:10.1038/boneres.2016.5

Cited by 48 publications

(45 citation statements)

References 98 publications

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“…The analysis of potential changes in gene expression of BMP type I and type II receptors showed that PEMFs or BMP2 used alone or in combination could increase ALK2 expression in the middle late phase of cell differentiation. This result appears of interest because of the key role of ALK2 in the osteogenic differentiation induced by several osteogenic BMPs and suggests that PEMFs and BMP2 may act through a modulation in BMP2 or BMP6 utilization as these BMPs predominantly act by this type I receptor in hMSCs [32,33]. Further, our observation is in agreement with previous studies showing that ALK2 expression may be upregulated through BMP/SMAD signaling in MSCs [34].…”

Section: Discussionsupporting

confidence: 92%

Bone Morphogenetic Protein-2 Signaling in the Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells Induced by Pulsed Electromagnetic Fields

Martini

Pellati

Mazzoni

et al. 2020

IJMS

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Pulsed electromagnetic fields (PEMFs) are clinically used with beneficial effects in the treatment of bone fracture healing. This is due to PEMF ability to favor the osteogenic differentiation of mesenchymal stem cells (MSCs). Previous studies suggest that PEMFs enhance the osteogenic activity of bone morphogenetic protein-2 (BMP2) which is used in various therapeutic interventions. This study investigated the molecular events associated to the synergistic activity of PEMFs and BMP2 on osteogenic differentiation. To this aim, human MSCs (hMSCs) were exposed to PEMFs (75 Hz, 1.5 mT) in combination with BMP2, upon detection of the minimal dose able to induce differentiation. Changes in the expression of BMP signaling pathway genes including receptors and ligands, as well as in the phosphorylation of BMP downstream signaling proteins, such as SMAD1/5/8 and MAPK, were analyzed. Results showed the synergistic activity of PEMFs and BMP2 on osteogenic differentiation transcription factors and markers. The PEMF effects were associated to the increase in BMP2, BMP6, and BMP type I receptor gene expression, as well as SMAD1/5/8 and p38 MAPK activation. These results increase knowledge concerning the molecular events involved in PEMF stimulation showing that PEMFs favor hMSCs osteogenic differentiation by the modulation of BMP signaling components.

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Section: Discussionsupporting

confidence: 92%

Bone Morphogenetic Protein-2 Signaling in the Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells Induced by Pulsed Electromagnetic Fields

Martini

Pellati

Mazzoni

et al. 2020

IJMS

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“…After bioinformatics analysis, we ltered that ACVR1, also known as ALK2, a member of bone morphogenetic protein receptors type I, was another target of bta-miR-365-3p. As an essential member of TGF-β family, ACVR1 has been reported to play functional roles in early embryonic development [48], lens formation [49], chondrogenesis, osteogenesis [50,51] and cardiac hypertrophy [52]. Additionally, recurrent heterozygous mutations of ACVR1 have been associated with diseases in human such as bro dysplasia ossi cans progress (FOP) [53], diffuse intrinsic pontine gliomas (DIPGs) [54] and pediatric midline high-grade astrocytoma (mHGAs) [55].…”

Section: Gene Targets Of Mir-365-3pmentioning

confidence: 99%

MicroRNA bta-miR-365-3p inhibits proliferation but promotes differentiation of primary bovine myoblasts by targeting the activin A receptor type I

Hao¹,

Wang

et al. 2020

Preprint

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Background: MicroRNAs act as post-transcriptional regulators that repress translation or degrades mRNA transcripts. Each microRNA has many mRNA targets and each mRNA may be targeted by several microRNAs. Skeletal muscles express a plethora of microRNA genes that regulate muscle development and function by controlling the expression of protein-coding target genes. To expand our understanding of the role of microRNA, specifically bta-miR-365-3p, in muscle biology, we studied its function in regulating primary bovine myoblast proliferation and differentiation.Results: We first show that bta-miR-365-3p is predominantly expressed in skeletal muscle and heart tissue in Chinese Qinchuan beef cattle. Quantitative PCR and western blotting showed that overexpression of bta-miR-365-3p significantly reduced the levels of cyclinD1 (CCND1), cyclin dependent kinase 2 (CDK2) and proliferating cell nuclear antigen (PCNA) but stimulated the expression of muscle differentiation markers MYOD1, MYOG, both at mRNA and protein level. Moreover, downregulation of bta-miR-365-3p increased the expression of CCND1, CDK2 and PCNA but decreased the expression of MYOD1 and MYOG at both mRNA and protein levels. Furthermore, flow cytometry, EdU proliferation assays and immunostaining showed that increased levels of bta-miR-365-3p suppressed cell proliferation but promoted myotube formation, whereas a decreased level of bta-miR-365-3p had opposite consequences. Finally, we determined that activin A receptor type I (ACVR1) is a direct target of bta-miR-365-3p. Thus, dual luciferase gene reporter assays demonstrated that bta-miR-365-3p can bind to the 3'UTR of ACVR1 gene to regulate its expression. Consistently, knock-down of ACVR1 was associated with reduced CDK2, CCND1 and PCNA expression but increased MYOG and MYOD1 expression both at mRNA and protein level.Conclusion: Collectively these data suggest that bta-miR-365-3p represses proliferation but promotes differentiation of bovine myoblasts through a mechanism involving downregulation of ACVR1.

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“…After bioinformatics analysis, we identi ed that ACVR1, also known as ALK2, a member of bone morphogenetic protein receptors type I, was another target of bta-miR-365-3p. As an essential member of TGF-β family, ACVR1 has the functional roles in early embryonic development [48], lens formation [49], chondrogenesis, osteogenesis [50,51] and cardiac hypertrophy [52]. Additionally, recurrent heterozygous mutations of ACVR1 were associated with diseases in human such as bro dysplasia ossi cans progress (FOP) [53], diffuse intrinsic pontine gliomas (DIPGs) [54] and pediatric midline high-grade astrocytoma (mHGAs) [55].…”

Section: Gene Targets Of Mir-365-3pmentioning

confidence: 99%

MicroRNA bta-miR-365-3p inhibits proliferation but promotes differentiation of primary bovine myoblasts by targeting the activin A receptor type I

Hao¹,

Wang

et al. 2020

Preprint

View full text Add to dashboard Cite

Background: MicroRNAs act as post-transcriptional regulators that repress translation or degrades mRNA transcripts. Each microRNA has many mRNA targets and each mRNA may be targeted by several microRNAs. Skeletal muscles express a plethora of microRNA genes that regulate muscle development and function by controlling the expression of protein-coding target genes. To expand our understanding of the role of microRNA, specifically bta-miR-365-3p, in muscle biology, we investigated its functions in regulating primary bovine myoblast proliferation and differentiation.Results: Firstly, we found that bta-miR-365-3p was predominantly expressed in skeletal muscle and heart tissue in Chinese Qinchuan beef cattle. Quantitative PCR and western blotting results showed that overexpression of bta-miR-365-3p significantly reduced the expression levels of cyclinD1 (CCND1), cyclin dependent kinase 2 (CDK2) and proliferating cell nuclear antigen (PCNA) but stimulated the expression levels of muscle differentiation markers, i.e., MYOD1, MYOG at both mRNA and protein level. Moreover, downregulation of bta-miR-365-3p increased the expression of CCND1, CDK2 and PCNA but decreased the expression of MYOD1 and MYOG at both mRNA and protein levels. Furthermore, flow cytometry, EdU proliferation assays and immunostaining results showed that increased levels of bta-miR-365-3p suppressed cell proliferation but promoted myotube formation, whereas decreased levels of bta-miR-365-3p resulted in the opposite consequences. Finally, we identified that activin A receptor type I (ACVR1) could be a direct target of bta-miR-365-3p. It was demonstrated that bta-miR-365-3p can bind to the 3'UTR of ACVR1 gene to regulate its expression based on dual luciferase gene reporter assays. Consistently, knock-down of ACVR1 was associated with decreased expressions of CDK2, CCND1 and PCNA but increased expression of MYOG and MYOD1 both at mRNA and protein level. Conclusion: Collectively, these data suggested that bta-miR-365-3p represses proliferation but promotes differentiation of bovine myoblasts through several biological mechanisms involving downregulation of ACVR1.

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The biological function of type I receptors of bone morphogenetic protein in bone

Cited by 48 publications

References 98 publications

Bone Morphogenetic Protein-2 Signaling in the Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells Induced by Pulsed Electromagnetic Fields

Bone Morphogenetic Protein-2 Signaling in the Osteogenic Differentiation of Human Bone Marrow Mesenchymal Stem Cells Induced by Pulsed Electromagnetic Fields

MicroRNA bta-miR-365-3p inhibits proliferation but promotes differentiation of primary bovine myoblasts by targeting the activin A receptor type I

MicroRNA bta-miR-365-3p inhibits proliferation but promotes differentiation of primary bovine myoblasts by targeting the activin A receptor type I

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