FAK mediates BMP9-induced osteogenic differentiation via Wnt and MAPK signaling pathway in synovial mesenchymal stem cells

Zheng, Weiwei; Gu, Xueping; Sun, Xingwei; Wu, Qin; Hu, Dan

doi:10.1080/21691401.2019.1631838

Cited by 24 publications

(20 citation statements)

References 41 publications

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“…Pcdhs could also modulate the activity of kinases and phosphatases that play a role in Wnt signaling. For instance, signaling downstream of Fak and Pyk2 has been linked to several Wnt pathway modules ( Chen et al, 2002 ; Gao et al, 2015 , 2019 ; Sun et al, 2016 ; Zheng et al, 2019 ).…”

Section: Signaling Downstream Of Pcdhsmentioning

confidence: 99%

Protocadherins at the Crossroad of Signaling Pathways

Pancho

Aerts

Mitsogiannis

et al. 2020

Front. Mol. Neurosci.

101

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Protocadherins (Pcdhs) are cell adhesion molecules that belong to the cadherin superfamily, and are subdivided into clustered (cPcdhs) and non-clustered Pcdhs (ncPcdhs) in vertebrates. In this review, we summarize their discovery, expression mechanisms, and roles in neuronal development and cancer, thereby highlighting the context-dependent nature of their actions. We furthermore provide an extensive overview of current structural knowledge, and its implications concerning extracellular interactions between cPcdhs, ncPcdhs, and classical cadherins. Next, we survey the known molecular action mechanisms of Pcdhs, emphasizing the regulatory functions of proteolytic processing and domain shedding. In addition, we outline the importance of Pcdh intracellular domains in the regulation of downstream signaling cascades, and we describe putative Pcdh interactions with intracellular molecules including components of the WAVE complex, the Wnt pathway, and apoptotic cascades. Our overview combines molecular interaction data from different contexts, such as neural development and cancer. This comprehensive approach reveals potential common Pcdh signaling hubs, and points out future directions for research. Functional studies of such key factors within the context of neural development might yield innovative insights into the molecular etiology of Pcdh-related neurodevelopmental disorders.

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Section: Signaling Downstream Of Pcdhsmentioning

confidence: 99%

Protocadherins at the Crossroad of Signaling Pathways

Pancho

Aerts

Mitsogiannis

et al. 2020

Front. Mol. Neurosci.

101

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“…In this study, we attempted to determine whether the LV-BMP9-infected BMSCs integrating P3HB4HB benefit the regeneration of defected skull bones. As previous studies described [ 29 , 30 ], the BMP9 molecule, a member of the BMP protein family, is the most effective inducer for triggering osteogenesis of BMSCs. Recent studies [ 31 , 32 ] also demonstrated that BMP9 administration remarkably promotes the regeneration and repair of injured bones.…”

Section: Discussionmentioning

confidence: 98%

A Composite Tissue Engineered Bone Material Consisting of Bone Mesenchymal Stem Cells, Bone Morphogenetic Protein 9 (BMP9) Gene Lentiviral Vector, and P3HB4HB Thermogel (BMSCs-LV-BMP9-P3HB4HB) Repairs Calvarial Skull Defects in Rats by Expression of Osteogenic Factors

Zhou

Zhao

et al. 2020

Med Sci Monit

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Background Bone tissue engineering has been proven to be an appropriate approach for treating bone defects. This study aimed to investigate the effects and mechanism of a composite tissue engineered bone material consisting of bone mesenchymal stem cells (BMSCs), bone morphogenetic protein (BMP9) gene lentiviral vector, and P3HB4HB thermogel (BMSCs-LV-BMP9-P3HB4HB) on calvarial skull defects in rats. Material/Methods LV-BMP9 viral vector was structured and infected to BMSCs-P3HB4HB composite scaffold, which was named as BMSCs-P3HB4HB composite bone repair material. Adipogenic differentiation was determined by oil-red O (ORO) and alkaline phosphatase (ALP) staining. Osteogenic differentiation was measured using Alizarin red staining. Cell viability was examined using Cell-Counting Kit-8 (CCK-8) assay. Protein expression of osteogenic factors, including BMP9, runt-related transcription factor 2 (RUNX2), osteocalcin (OCN), osteopontin (OPN), and osterix (OSX), was detected with Western blot assay and immunohistochemistry. mRNA of these osteogenic factors was examined by RT-PCR. Histological changes were examined with hematoxylin and eosin (H&E) and Masson’s trichrome staining. Bone repair was measured using micro-computed tomography (micro-CT). Results BMSCs and LV-BMP9-infected BMSCs demonstrated adipogenic and osteogenic differentiation potential. BMSCs-P3HB4HB scaffold demonstrated good cell-tissue compatibility. BMSCs-LV-BMP9-P3HB4HB exhibited significantly higher osteogenic ability and cell viability of BMSCs compared to BMSCs-LV-P3HB4HB ( p <0.05). BMSCs-LV-BMP9-P3HB4HB significantly promoted osteogenic factors (RUNX2, OCN, OPN, and OSX) expression compared to the BMSCs-LV-P3HB4HB group ( p <0.05) in both BMSCs and in calvarial defect rats. BMSCs-LV-BMP9-P3HB4HB demonstrated stronger repair ability. BMSCs-LV-BMP9-P3HB4HB significantly alleviated pathological injury and increased collagen fiber production compared to the BMSCs-LV-P3HB4HB group ( p <0.05). Conclusions BMSCs-LV-BMP9-P3HB4HB composite bone repair material can effectively repair injured skull tissues of calvarial defect rats through triggering osteogenic factors expression. The present generated bone repair material may have applications in tissue engineering in regeneration of bone defects.

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“…Co-cultured with miR-889 inhibitor and WNT7Ai were associated with a reduction of the calcium deposition than miR-889 alone and also increased than NC group. Zheng et al [22] found that disturbing the Wnt-β catenin signaling pathway could impair the osteogenesis of hBMMSCs. Our results were in accordance with previous findings.…”

Section: Discussionmentioning

confidence: 99%

The mechanism of miR-889 regulates osteogenesis in human bone marrow mesenchymal stem cells

Ding

Shi

2019

J Orthop Surg Res

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Background: Bone marrow mesenchymal stem cells (BMMSCs) can be used for bone regeneration in the specified condition. Osteogenic differentiation of BMMSCs is controlled by microRNAs (miRNAs) and other factors. This study was aimed to identify the role and mechanism of miR-889 in regulating the osteogenic differentiation of BMMSCs. Methods: Osteoporosis patients and normal control bone tissues were collected and used PCR techniques to identify the change of miR-889 and WNT7A. Moreover, the dynamic change of miR-889 and WNT7A during osteogenic differentiation of BMMSCs was also measured. Bioinformatic analysis was performed to identify the target genes and potential pathways of miR-889. Then, we constructed miR-889 mimic and inhibitor, ALP staining, ARS, osteoblastic-related protein, and Wnt β-catenin signaling pathway-related protein were also measured. WNT7A siRNA was also used to verify the function of miR-889. Results: In the present study, we showed that miR-889 expression was upregulated in osteoporosis patients than healthy control. However, the miR-889 expression was downregulated during osteogenic differentiation. Bioinformatics analysis found that miR-889 targets 666 genes and mainly through Wnt β-catenin signaling pathway. Administrated miR-889 mimic, the ALP activity, and calcium deposition were decreased than the control group, while miR-889 inhibitor shown the opposite trend. And miR-889 could bind the 3′UTR of WNT7A. We further used WNT7A siRNA to explore the function of miR-889, and the results revealed that co-cultured with miR-889 inhibitor and WNT7A siRNA was associated with a reduction of ALP activity and calcium deposition and osteoblastic-related proteins than miR-889 inhibitor alone. Conclusion: Our results revealed that miR-889 plays a negative role in inducing osteogenic differentiation of BMSCs through Wnt β-catenin signaling pathway.

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FAK mediates BMP9-induced osteogenic differentiation via Wnt and MAPK signaling pathway in synovial mesenchymal stem cells

Cited by 24 publications

References 41 publications

Protocadherins at the Crossroad of Signaling Pathways

Protocadherins at the Crossroad of Signaling Pathways

A Composite Tissue Engineered Bone Material Consisting of Bone Mesenchymal Stem Cells, Bone Morphogenetic Protein 9 (BMP9) Gene Lentiviral Vector, and P3HB4HB Thermogel (BMSCs-LV-BMP9-P3HB4HB) Repairs Calvarial Skull Defects in Rats by Expression of Osteogenic Factors

The mechanism of miR-889 regulates osteogenesis in human bone marrow mesenchymal stem cells

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