Src enhances osteogenic differentiation through phosphorylation of Osterix

Choi, You Hee; Han, Youn Ho; Lee, Sung Ho; Cheong, Heesun; Chun, Kwang Hoon; Yeo, Chang Yeol; Lee, Kwang Youl

doi:10.1016/j.mce.2015.03.010

Cited by 19 publications

(15 citation statements)

References 55 publications

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“…(2015) demonstrated that, in addition to adhesive properties, exosomal integrin uptake can activate SRC in specific resident cells. SRC is an upstream signaling partner of ERK and regulates SMAD nuclear translation through activation of osterix and results in osteoblastic bone mineralization (Choi et al., 2015). These integrin‐related proteins were largely downregulated in SDEs of osteoporosis patients in this study.…”

Section: Discussionmentioning

confidence: 99%

Involvement of serum‐derived exosomes of elderly patients with bone loss in failure of bone remodeling via alteration of exosomal bone‐related proteins

et al. 2018

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SummaryExosomes are secreted into the blood by various types of cells. These extracellular vesicles are involved in the contribution of exosomal proteins to osteoblastic or osteoclastic regulatory networks during the failure of bone remodeling, which results in age‐related bone loss. However, the molecular changes in serum‐derived exosomes (SDEs) from aged patients with low bone density and their functions in bone remodeling remain to be fully elucidated. We present a quantitative proteomics analysis of exosomes purified from the serum of the elderly patients with osteoporosis/osteopenia and normal volunteers; these data are available via Proteome Xchange with the identifier PXD006463. Overall, 1,371 proteins were identified with an overlap of 1,160 Gene IDs among the ExoCarta proteins. Bioinformatics analysis and in vitro studies suggested that protein changes in SDEs of osteoporosis patients are not only involved in suppressing the integrin‐mediated mechanosensation and activation of osteoblastic cells, but also trigger the differentiation and resorption of osteoclasts. In contrast, the main changes in SDEs of osteopenia patients facilitated both activation of osteoclasts and formation of new bone mass, which could result in a compensatory elevation in bone remodeling. While the SDEs from aged normal volunteers might play a protective role in bone health through facilitating adhesion of bone cells and suppressing aging‐associated oxidative stress. This information will be helpful in elucidating the pathophysiological functions of SDEs and aid in the development of senile osteoporosis diagnostics and therapeutics.

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Section: Discussionmentioning

confidence: 99%

Involvement of serum‐derived exosomes of elderly patients with bone loss in failure of bone remodeling via alteration of exosomal bone‐related proteins

et al. 2018

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“…In line with this consideration, miR-203 was suggested to target c-Abl, as the protein expression level of the latter is inflected by an ectopic modulation of the expression of this miRNA [204]. In addition, it was shown that the kinase capabilities of the SRC protein implicated it in osteoblastic differentiation, as it helps stabilize Osterix, consequently increasing the transcriptional activity of this factor [205]. Interestingly, Wang et al showed that miR-203 directly targets SRC in a lung cancer model ( Figure 6) [206].…”

Section: The C-jun N-terminal Kinase/p38 (Jnk/p38) and Mitogen-activamentioning

confidence: 88%

Implication of the p53-Related miR-34c, -125b, and -203 in the Osteoblastic Differentiation and the Malignant Transformation of Bone Sarcomas

Jacques

Tesfaye

Lavaud

et al. 2020

Cells

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The formation of the skeleton occurs throughout the lives of vertebrates and is achieved through the balanced activities of two kinds of specialized bone cells: the bone-forming osteoblasts and the bone-resorbing osteoclasts. Impairment in the remodeling processes dramatically hampers the proper healing of fractures and can also result in malignant bone diseases such as osteosarcoma. MicroRNAs (miRNAs) are a class of small non-coding single-strand RNAs implicated in the control of various cellular activities such as proliferation, differentiation, and apoptosis. Their post-transcriptional regulatory role confers on them inhibitory functions toward specific target mRNAs. As miRNAs are involved in the differentiation program of precursor cells, it is now well established that this class of molecules also influences bone formation by affecting osteoblastic differentiation and the fate of osteoblasts. In response to various cell signals, the tumor-suppressor protein p53 activates a huge range of genes, whose miRNAs promote genomic-integrity maintenance, cell-cycle arrest, cell senescence, and apoptosis. Here, we review the role of three p53-related miRNAs, miR-34c, -125b, and -203, in the bone-remodeling context and, in particular, in osteoblastic differentiation. The second aim of this study is to deal with the potential implication of these miRNAs in osteosarcoma development and progression.

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“…These studies also showed that BMP-2 induction of Osx required the transcriptional activation of Dlx5 by p38 MAPK-mediated phosphorylation 27 28 . Moreover, additional pathways may act in parallel to, or independent of Osx transcription to post-transcriptionally modulate the function of Osx through phosphorylation, regulation of protein stability, and transcriptional activity 29 30 31 . However, in contrast to our understanding of bone biology with BMPs, the molecular mechanisms by which the expression of Osx can be regulated by TGF-β in cementogenesis remain unclear.…”

Section: Discussionmentioning

confidence: 99%

TGF-β Signaling Regulates Cementum Formation through Osterix Expression

Choi

Ahn

Kim

et al. 2016

Sci Rep

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TGF-β/BMPs have widely recognized roles in mammalian development, including in bone and tooth formation. To define the functional relevance of the autonomous requirement for TGF-β signaling in mouse tooth development, we analyzed osteocalcin-Cre mediated Tgfbr2 (OCCreTgfbr2fl/fl) conditional knockout mice, which lacks functional TGF-β receptor II (TβRII) in differentiating cementoblasts and cementocytes. Strikingly, OCCreTgfbr2fl/fl mutant mice exhibited a sharp reduction in cellular cementum mass with reduced matrix secretion and mineral apposition rates. To explore the molecular mechanisms underlying the roles of TGF-β signaling through TβRII in cementogenesis, we established a mouse cementoblast model with decreased TβRII expression using OCCM-30 cells. Interestingly, the expression of osterix (Osx), one of the major regulators of cellular cementum formation, was largely decreased in OCCM-30 cells lacking TβRII. Consequently, in those cells, functional ALP activity and the expression of genes associated with cementogenesis were reduced and the cells were partially rescued by Osx transduction. We also found that TGF-β signaling directly regulates Osx expression through a Smad-dependent pathway. These findings strongly suggest that TGF-β signaling plays a major role as one of the upstream regulators of Osx in cementoblast differentiation and cementum formation.

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Src enhances osteogenic differentiation through phosphorylation of Osterix

Cited by 19 publications

References 55 publications

Involvement of serum‐derived exosomes of elderly patients with bone loss in failure of bone remodeling via alteration of exosomal bone‐related proteins

Involvement of serum‐derived exosomes of elderly patients with bone loss in failure of bone remodeling via alteration of exosomal bone‐related proteins

Implication of the p53-Related miR-34c, -125b, and -203 in the Osteoblastic Differentiation and the Malignant Transformation of Bone Sarcomas

TGF-β Signaling Regulates Cementum Formation through Osterix Expression

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