Dataset Information

CUEDC2 controls osteoblast differentiation and bone formation via SOCS3-STAT3 pathway.

ABSTRACT: The CUE domain-containing 2 (CUEDC2) protein plays critical roles in many biological processes, such as the cell cycle, inflammation, and tumorigenesis. However, whether CUEDC2 is involved in osteoblast differentiation and plays a role in bone regeneration remains unknown. This study investigated the role of CUEDC2 in osteogenesis and its underlying molecular mechanisms. We found that CUEDC2 is expressed in bone tissues. The expression of CUEDC2 decreased during bone development and BMP2-induced osteoblast differentiation. The overexpression of CUEDC2 suppressed the osteogenic differentiation of precursor cells, while the knockdown of CUEDC2 showed the opposite effect. In vivo studies showed that the overexpression of CUEDC2 decreased bone parameters (bone volume, bone area, and bone mineral density) during ectopic bone formation, whereas its knockdown increased bone volume and the reconstruction percentage of critical-size calvarial defects. We found that CUEDC2 affects STAT3 activation by regulating SOCS3 protein stability. Treatment with a chemical inhibitor of STAT3 abolished the promoting effect of CUEDC2 silencing on osteoblast differentiation. Together, we suggest that CUEDC2 functions as a key regulator of osteoblast differentiation and bone formation by targeting the SOCS3-STAT3 pathway. CUEDC2 manipulation could serve as a therapeutic strategy for controlling bone disease and regeneration.

SUBMITTER: Kim JW

PROVIDER: S-EPMC7214468 | biostudies-literature | 2020 May

REPOSITORIES: biostudies-literature

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CUEDC2 controls osteoblast differentiation and bone formation via SOCS3-STAT3 pathway.

Kim Jung-Woo JW Oh Sin-Hye SH Lee Mi Nam MN Song Ju Han JH Jeong Byung-Chul BC Yang Jin-Woo JW Piao Xianyu X Zang Yaran Y Ryu Je-Hwang JH Koh Jeong-Tae JT

Cell death & disease 20200511 5

The CUE domain-containing 2 (CUEDC2) protein plays critical roles in many biological processes, such as the cell cycle, inflammation, and tumorigenesis. However, whether CUEDC2 is involved in osteoblast differentiation and plays a role in bone regeneration remains unknown. This study investigated the role of CUEDC2 in osteogenesis and its underlying molecular mechanisms. We found that CUEDC2 is expressed in bone tissues. The expression of CUEDC2 decreased during bone development and BMP2-induced ...[more]

PMID: 32393737

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Project description:The Pacific oyster, Crassostrea gigas, is well-known as a nutritious food. Recently, we revealed that fermented extract of C. gigas (FO) inhibited ovariectomy-induced osteoporosis, resulting from suppression of osteoclastogenesis. However, since the beneficial effect of FO on osteogenesis is poorly understood, it was examined in mouse preosteoblast MC3T3-E1 cells, human osteosarcoma MG-63 osteoblast-like cells, and zebrafish larvae in this study. We found that FO increased mitochondrial activity from days 1 to 7; however, total cell number of MC3T3-E1 cells gradually decreased without any change in cell viability, which suggests that FO stimulates the differentiation of MC3T3-E1 cells. FO also promoted the expression of osteoblast marker genes, including runt-related transcription factor 2 (mRUNX2), alkaline phosphatase (mALP), collagen type I ?1 (mCol1?1), osteocalcin (mOCN), osterix (mOSX), bone morphogenetic protein 2 (mBMP2), and mBMP4 in MC3T3-E1 cells accompanied by a significant increase in ALP activity. FO also increased nuclear translocation of RUNX2 and OSX transcription factors, ALP activity, and calcification in vitro along with the upregulated expression of osteoblast-specific marker proteins such as RUNX2, ALP, Col1?1, OCN, OSX, and BMP4. Additionally, FO enhanced bone mineralization (calcein intensity) in zebrafish larvae at 9 days post-fertilization comparable to that in the ?-glycerophosphate (GP)-treated group. All the tested osteoblast marker genes, including zRUNX2a, zRUNX2b, zALP, zCol1a1, zOCN, zBMP2, and zBMP4, were also remarkably upregulated in the zebrafish larvae in response to FO. It also promoted tail fin regeneration in adult zebrafish as same as the GP-treated groups. Furthermore, not only FO positively regulate ?-catenin expression and Wnt/?-catenin luciferase activity, but pretreatment with a Wnt/?-catenin inhibitor (FH535) also significantly decreased FO-mediated bone mineralization in zebrafish larvae, which indicates that FO-induced osteogenesis depends on the Wnt/?-catenin pathway. Altogether, the current study suggests that the supplemental intake of FO has a beneficial effect on osteogenesis.

Dataset Information

CUEDC2 controls osteoblast differentiation and bone formation via SOCS3-STAT3 pathway.

Publications

CUEDC2 controls osteoblast differentiation and bone formation via SOCS3-STAT3 pathway.

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