Glucocorticoid-induced gene tripartite motif-containing 63 (TRIM63) promotes differentiation of osteoblastic cells

Azuma, Kotaro; Urano, Tomohiko; Ouchi, Yasuyoshi; Inoue, Satoshi

doi:10.1507/endocrj.k09e-290

Cited by 18 publications

(11 citation statements)

References 25 publications

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“…The underlying mechanisms are unclear. Despite studies that show low‐dose GCs are positive regulators of bone formation in vitro or in vivo experiments [Kalak et al, ; Azuma et al, ]; they clearly inhibit bone formation in clinical therapy. Some researchers reported that GCs can induce adipogenic differentiation in bone marrow mesenchymal cells and can suppress their proliferation [Lin et al, ].…”

Section: Introductionmentioning

confidence: 99%

The effect of electromagnetic fields on the proliferation and the osteogenic or adipogenic differentiation of mesenchymal stem cells modulated by dexamethasone

Song

Zhao

Wei

et al. 2014

Bioelectromagnetics

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Although glucocorticoids provide benefits for inflammation or autoimmune disorders, high-dose and long-term use could cause osteonecrosis or osteoporosis as adverse effect for patients. Electromagnetic field (EMF) treatments have been clinically used for many years to promote fracture healing, but whether EMF can attenuate the deleterious effects of glucocorticoids is not clear. In this study, the effects of different concentrations of dexamethasone (DEX) on proliferation and adipogenic or osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) were detected and compared, and the effects of EMF treatment (15 Hz, 1 mT, 4 h/day) on 0.1 µM DEX-modulated BMSCs' proliferation and adipogenic or osteogenic differentiation were investigated. Higher concentrations of DEX (0.1 and 1 µM) inhibited proliferation of BMSCs but promoted expression of adipogenic-related genes, increasing the number of lipid droplets. In the early stage of differentiation, DEX restrained expression of RUNX2 and alkaline phosphatase (ALP), but amplified expression of ALP and osteopontin (OPN) in the late stage. EMF treatment of BMSCs influenced by 0.1 µM DEX inhibited the high expression of adipogenic-related genes, stimulated the expression of RUNX2, ALP, OPN, and osteocalcin, and increased the activity of ALP. EMF exposure augmented the expression of p-ERK, which DEX reduced. After using mitogen-activated protein/extracellular signal-regulated kinase (ERK) kinase (MEK)/ERK signaling pathway inhibitor, U0126, the effect of EMF was reduced. In conclusion, EMF exposure accelerates BMSCs proliferation, inhibits adipogenic differentiation, and promotes osteogenic differentiation of BMSCs modulated by DEX, and these effects are mediated at least in part by MEK/ERK signaling pathway.

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Section: Introductionmentioning

confidence: 99%

The effect of electromagnetic fields on the proliferation and the osteogenic or adipogenic differentiation of mesenchymal stem cells modulated by dexamethasone

Song

Zhao

Wei

et al. 2014

Bioelectromagnetics

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“…TRIM63, also termed muscle-specific ring finger protein 1, has been reported as an E3 ubiquitin ligase expressed predominantly in muscular tissue. Azuma et al ( 35 ) proposed that the overexpression of TRIM63 increased the expression of an osteoblastic differentiation marker gene, alkaline phosphatase, resulting in reduced proliferation. In addition, TRIM63 was identified to be involved in the two major bone remodeling activities, osteoblastic bone formation and osteoclastic bone resorption ( 36 ).…”

Section: Discussionmentioning

confidence: 99%

In silico analysis of the molecular mechanism of postmenopausal osteoporosis

Liu

Wang

Yang

et al. 2015

Molecular Medicine Reports

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Postmenopausal osteoporosis (PO) is a common disease in females >50 years of age worldwide and is becoming an increasing burden to society. The present study aimed to assess the molecular mechanism of PO using bioinformatic methods. The gene expression data from patients with PO and normal controls were downloaded from the ArrayExpress database provided by European Bioinformatics Institute. Following the screening of the differentially expressed genes (DEGs) using the Limma package in R language, Kyoto Encyclopedia of Genes and Genomes pathways enrichment analysis was performed using the Database for Annotation, Visualization and Integrated Discovery online tools. Sequentially, modulators of the DEGs, including transcription factors (TFs) and microRNAs, were predicted by the ChIP Enrichment Analysis databases and WEB-based GEne SeT AnaLysis Toolkit system, respectively. In addition, the protein-protein interaction network of DEGs was constructed via the search tool for the retrieval of interacting genes and then the functional modules were further analyzed via the cluster-Maker package and The Biological Networks Gene Ontology package within the Cytoscape software. A total of 482 DEGs, including 279 upregulated and 203 downregulated DEGs, were screened out. DEGs were predominantly enriched in the pathways of fatty acid metabolism, cardiac muscle contraction and DNA replication. TFs, including SMAD4, in addition to microRNAs, including the microRNA-125 (miR-125) family, miR-331 and miR-24, may be the modulators of the DEGs in PO. In addition, the five largest modules were identified with TTN, L1G1, ACADM, UQCRC2 and TRIM63 as the hub proteins, and they were associated with the biological processes of muscle contraction, DNA replication initiation, lipid modification, generation of precursor metabolites and energy, and regulation of acetyl-CoA biosynthetic process, respectively. SMAD4, CACNG1 and TRIM63 are suggested to be important factors in the molecular mechanisms of PO, and miR-331 may be novel potential biomarker for PO.

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“…The point mutants of HSP70 (K71S and V438F) and HSP90 (D88N) were created using PCR-based targeted mutagenesis and confirmed with DNA sequence analysis. The expression plasmids for HSP40 (HDJ1; [22]) and FLAG-TRIM63 [23] were provided by Drs. Ohtsuka (Gifu University) and Inoue (University of Tokyo), respectively.…”

Section: Methodsmentioning

confidence: 99%

TRIM32-Cytoplasmic-Body Formation Is an ATP-Consuming Process Stimulated by HSP70 in Cells

et al. 2017

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The spontaneous and energy-releasing reaction of protein aggregation is typically prevented by cellular quality control machinery (QC). TRIM32 is a member of the TRIM (tripartite motif-containing) ubiquitin E3 ligases, and when overexpressed in cultured cells, readily forms spherical inclusions designated as cytoplasmic bodies (CBs) even without proteasome inhibition. Here, we show that HSP70, a central QC component, is a primary binding factor of overexpressed TRIM32. Contrary to expectation, however, we find that this molecular chaperone facilitates and stabilizes CB assembly depending on intrinsic ATPase activity, rather than preventing CB formation. We also show that the HSP70-TRIM32 complex is biochemically distinct from the previously characterized 14-3-3-TRIM32 phospho-complex. Moreover, the two complexes have opposing roles, with HSP70 stimulating CB formation and 14-3-3 retaining TRIM32 in a diffuse form throughout the cytosol. Our results suggest that CB inclusion formation is actively controlled by cellular QC and requires ATP, similar to protein folding and degradation reactions.

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Glucocorticoid-induced gene tripartite motif-containing 63 (TRIM63) promotes differentiation of osteoblastic cells

Cited by 18 publications

References 25 publications

The effect of electromagnetic fields on the proliferation and the osteogenic or adipogenic differentiation of mesenchymal stem cells modulated by dexamethasone

The effect of electromagnetic fields on the proliferation and the osteogenic or adipogenic differentiation of mesenchymal stem cells modulated by dexamethasone

In silico analysis of the molecular mechanism of postmenopausal osteoporosis

TRIM32-Cytoplasmic-Body Formation Is an ATP-Consuming Process Stimulated by HSP70 in Cells

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