The dynamic skeleton

Gonciulea, Anda; Beur, Suzanne Jan de

doi:10.1007/s11154-015-9316-1

Cited by 14 publications

(11 citation statements)

References 121 publications

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“…Bone is a dynamic organ that undergoes continuous remodeling throughout life [16,17] and bone homeostasis is maintained by a balance between osteoclast-mediated bone resorption and osteoblast-mediated bone formation [18,19]. Osteoclasts are large multinucleated cells that develop from the monocyte-macrophage lineage [20].…”

Section: Introductionmentioning

confidence: 99%

METTL3 Modulates Osteoclast Differentiation and Function by Controlling RNA Stability and Nuclear Export

Cai

Meng

et al. 2020

IJMS

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Osteoclast differentiation and function are crucial for maintaining bone homeostasis and preserving skeletal integrity. N6-methyladenosine (m6A) is an abundant mRNA modification that has recently been shown to be important in regulating cell lineage differentiation. Nevertheless, the effect of m6A on osteoclast differentiation remains unknown. In the present study, we observed that the m6A level and methyltransferase METTL3 expression increased during osteoclast differentiation. Mettl3 knockdown resulted in an increased size but a decreased bone-resorbing ability of osteoclasts. The expression of osteoclast-specific genes (Nfatc1, c-Fos, Ctsk, Acp5 and Dcstamp) was inhibited by Mettl3 depletion, while the expression of the cellular fusion-specific gene Atp6v0d2 was upregulated. Mechanistically, Mettl3 knockdown elevated the mRNA stability of Atp6v0d2 and the same result was obtained when the m6A-binding protein YTHDF2 was silenced. Moreover, the phosphorylation levels of key molecules in the MAPK, NF-κB and PI3K-AKT signaling pathways were reduced upon Mettl3 deficiency. Depletion of Mettl3 maintained the retention of Traf6 mRNA in the nucleus and reduced the protein levels of TRAF6. Taken together, our data suggest that METTL3 regulates osteoclast differentiation and function through different mechanisms involving Atp6v0d2 mRNA degradation mediated by YTHDF2 and Traf6 mRNA nuclear export. These findings elucidate the molecular basis of RNA epigenetic regulation in osteoclast development.

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Section: Introductionmentioning

confidence: 99%

METTL3 Modulates Osteoclast Differentiation and Function by Controlling RNA Stability and Nuclear Export

Cai

Meng

et al. 2020

IJMS

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“…The proliferation and differentiation of mesenchymal stem cells toward osteoblasts is important for bone development and formation. The process involves in multiple regulatory signaling pathways and transcription factors [1,2]. Both canonical and non-canonical Wnt signaling pathways play essential roles in mesenchymal stem cells differentiation into osteoblasts along with their proliferation and mineralization [1,3,4].…”

Section: Introductionmentioning

confidence: 99%

Loss of receptor tyrosine kinase-like orphan receptor 2 impairs the osteogenesis of mBMSCs by inhibiting signal transducer and activator of transcription 3

et al. 2020

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Background: Receptor tyrosine kinase-like orphan receptor 2 (Ror2) plays a key role in bone formation, but its signaling pathway is not completely understood. Signal transducer and activator of transcription 3 (Stat3) takes part in maintaining bone homeostasis. The aim of this study is to reveal the role and mechanism of Ror2 in the osteogenic differentiation from mouse bone marrow mesenchymal stem cells (mBMSCs) and to explore the effect of Stat3 on Ror2-mediated osteogenesis. Methods: Ror2 CKO mice were generated via the Cre-loxp recombination system using Prrx1-Cre transgenic mice. Quantitative real-time PCR and western blot were performed to assess the expression of Stat3 and osteogenic markers in Ror2-knockdown mBMSCs (mBMSC-sh-Ror2). After being incubated in osteogenic induction medium for 3 weeks, Alizarin Red staining and western blot were used to examine the calcium deposit and osteogenic markers in Stat3 overexpression in mBMSC-sh-Ror2. Results: Loss of Ror2 in mesenchymal or osteoblast progenitor cells led to a dwarfism phenotype in vivo. The mRNA expression of osteogenic markers (osteocalcin, osteopontin (OPN), and collagen I) in the ulna proximal epiphysis of Ror2 CKO mice was significantly decreased (P < 0.05). The mRNA and protein expression of Stat3 and osteogenic markers (Runx2, osterix, and OPN) decreased in mBMSC-sh-Ror2 cells (P < 0.05). The overexpression of Stat3 in mBMSC-sh-Ror2 cells rescued the calcium deposit and expression of Runx2, osterix, and OPN to a level comparable to normal mBMSCs. Conclusions: Ror2 was essential for skeleton development by regulating mBMSCs' osteogenesis and osteoblast differentiation. Loss of Ror2 may impair the osteogenesis of mBMSCs by inhibiting Stat3.

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“…OPG and Runx2 are closed related to bone development and regeneration [30,31,32]. Runx2 is a major transcription factor involved in osteogenesis [31] and is essential for bone development and osteoblast differentiation from mesenchymal cells [59].…”

Section: Discussionmentioning

confidence: 99%

“…The regulation of TNF-α expression is an important therapeutic target for successfully grafting bone in patients with autoimmune disease [28,29]. Several markers have been shown to indicate bone regeneration, including fibroblast growth factor-23 (FGF-23), osteoprotegerin (OPG), and Runt-related transcription factor 2 (Runx2) [30,31,32]. …”

Section: Introductionmentioning

confidence: 99%

Silk Fibroin-Alginate-Hydroxyapatite Composite Particles in Bone Tissue Engineering Applications In Vivo

Kim

Kwon

et al. 2017

IJMS

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The aim of this study was to evaluate the in vivo bone regeneration capability of alginate (AL), AL/hydroxyapatite (HA), and AL/HA/silk fibroin (SF) composites. Forty Sprague Dawley rats were used for the animal experiments. Central calvarial bone (diameter: 8.0 mm) defects were grafted with AL, AL/HA, or AL/HA/SF. New bone formation was evaluated by histomorphometric analysis. To demonstrate the immunocompatibility of each group, the level of tumor necrosis factor (TNF)-α expression was studied by immunohistochemistry (IHC) and quantitative reverse transcription polymerase chain reaction (qRT-PCR) at eight weeks post implantation. Additionally, osteogenic markers, such as fibroblast growth factor (FGF)-23, osteoprotegerin (OPG), and Runt-related transcription factor (Runx2) were evaluated by qPCR or IHC at eight weeks post implantation. The AL/HA/SF group showed significantly higher new bone formation than did the control group (p = 0.044) and the AL group (p = 0.035) at four weeks post implantation. Additionally, the AL/HA/SF group showed lower relative TNF-α mRNA levels and higher FGF-23 mRNA levels than the other groups did at eight weeks post implantation. IHC results demonstrated that the AL/HA/SF group had lower TNF-α expression and higher OPG and Runx2 expression at eight weeks post implantation. Additionally, no evidence of the inflammatory reaction or giant cell formation was observed around the residual graft material. We concluded that the AL/HA/SF composite could be effective as a scaffold for bone tissue engineering.

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The dynamic skeleton

Cited by 14 publications

References 121 publications

METTL3 Modulates Osteoclast Differentiation and Function by Controlling RNA Stability and Nuclear Export

METTL3 Modulates Osteoclast Differentiation and Function by Controlling RNA Stability and Nuclear Export

Loss of receptor tyrosine kinase-like orphan receptor 2 impairs the osteogenesis of mBMSCs by inhibiting signal transducer and activator of transcription 3

Silk Fibroin-Alginate-Hydroxyapatite Composite Particles in Bone Tissue Engineering Applications In Vivo

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