Uncarboxylated osteocalcin reverses the high glucose‑induced inhibition of the osteogenic differentiation of MC3T3E1 cells via the GPRC6A/cAMP/PKA/AMPK signaling pathway

Ma, Luyao; Gong, Fangzi; Xu, Jiaojiao; Yang, Jianhong

doi:10.3892/ijmm.2021.4924

Cited by 4 publications

(3 citation statements)

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“…GPRC6A, thereby promoting the differentiation of pro-osteoblasts [47]. In the present experiments, we confirm that GPRC6A expression increases after the addition of GluOC in OA/PA-induced HepG2 cells.…”

Section: Discussionsupporting

confidence: 84%

“…GPRC6A, a widely expressed G-protein coupled receptor, is proposed to be a master regulator of complex endocrine networks and metabolic processes [ 46 ]. Our previous work has demonstrated that osteocalcin can activate AMPK through the putative receptor GPRC6A, thereby promoting the differentiation of pro-osteoblasts [ 47 ]. In the present experiments, we confirm that GPRC6A expression increases after the addition of GluOC in OA/PA-induced HepG2 cells.…”

Section: Discussionmentioning

confidence: 99%

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Uncarboxylated Osteocalcin Decreases SCD1 by Activating AMPK to Alleviate Hepatocyte Lipid Accumulation

Wang

Zhang

et al. 2023

Molecules

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Uncarboxylated osteocalcin (GluOC), a small-molecule protein specifically synthesized and secreted by osteoblasts, is important in the regulation of energy metabolism. In our previous study, GluOC was shown to be effective in ameliorating dyslipidemia and hepatic steatosis in KKAy mice. However, the underlying mechanism of GluOC action on hepatocytes has not been well validated. In this study, oleic acid/palmitic acid (OA/PA)-induced HepG2 and NCTC 1469 cells were used as non-alcoholic fatty liver disease (NAFLD) cell models, and triacylglycerol (TG) levels were measured by oil red O staining, Nile Red staining, and ELISA. The fatty acid synthesis-related protein expression was detected by real-time quantitative polymerase chain reaction, Western blotting, and immunofluorescence. The results show that GluOC reduced triglyceride levels, and decreased the expression of sterol regulatory element-binding protein-1c (SREBP-1c) and stearyl-coenzyme A desaturase 1 (SCD1). si-SCD1 mimicked the lipid accumulation-reducing effect of GluOC, while overexpression of SCD1 attenuated the effect of GluOC. In addition, GluOC activated AMP-activated protein kinase (AMPK) phosphorylation to affect lipid metabolism in hepatocytes. Overall, the results of this study suggest that GluOC decreases SCD1 by activating AMPK to alleviate hepatocyte lipid accumulation, which provides a new target for improving NAFLD in further research.

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Section: Discussionsupporting

confidence: 84%

Section: Discussionmentioning

confidence: 99%

Uncarboxylated Osteocalcin Decreases SCD1 by Activating AMPK to Alleviate Hepatocyte Lipid Accumulation

Wang

Zhang

et al. 2023

Molecules

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“…In addition, the absence of Caveolin-1 has been reported to activate the cAMP/PKA signaling to inhibit lipid droplet formation in endothelial cells (Kuo et al 2018). A recent study has reported the suppressing effect of activated cAMP/PKA pathway on the adipogenic differentiation of MC3T3E1 cells (Ma et al 2021). However, the inhibiting property of the cAMP/PKA pathway on the adipogenic differentiation of TSCs lacks available evidence to support and requires further studies.…”

Section: Discussionmentioning

confidence: 99%

Caveolin-1 is involved in fatty infiltration and bone-tendon healing of rotator cuff tear

Fang

You

Wang

et al. 2023

Mol Med

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Background Caveolin-1 has been predicted, based on RNA transcriptome sequencing, as a key gene in rotator cuff tear (RCT) and it is related to fatty infiltration. This study aims to elucidate the upstream and downstream mechanism of Caveolin-1 in fatty infiltration and bone-tendon healing after RCT in rat models. Methods Differentially expressed genes related to RCT were screened, followed by functional enrichment analysis and protein-protein interaction analysis. GATA6 was overexpressed and Caveolin-1 was knocked down in tendon stem cells (TSCs) to evaluate their effects on the adipogenic differentiation of TSCs. In addition, a RCT rat model was constructed and injected with lentivirus carrying oe-GATA6, oe-Caveolin-1 alone or in combination to assess their roles in fatty infiltration and bone-tendon healing. Results and conclusion Caveolin-1 was identified as a key gene involved in the RCT process. In vitro results demonstrated that Caveolin-1 knockdown inhibited adipogenic differentiation of TSCs by activating the cAMP/PKA pathway. GATA6 inhibited the transcription of Caveolin-1 and inhibited its expression, thus suppressing the adipogenic differentiation of TSCs. In vivo data confirmed that GATA6 overexpression activated the cAMP/PKA pathway by downregulating Caveolin-1 and consequently repressed fatty infiltration, promoted bone-tendon healing, improved biomechanical properties and reduced the rupture risk of injured tendon in rats after RCT. Overall, this study provides novel insights into the mechanistic action of Caveolin-1 in the fatty infiltration and bone-tendon healing after RCT.

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Zoledronate Promotes Peri-Implant Osteogenesis in Diabetic Osteoporosis by the AMPK Pathway

et al. 2023

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Uncarboxylated osteocalcin reverses the high glucose‑induced inhibition of the osteogenic differentiation of MC3T3E1 cells via the GPRC6A/cAMP/PKA/AMPK signaling pathway

Cited by 4 publications

References 0 publications

Uncarboxylated Osteocalcin Decreases SCD1 by Activating AMPK to Alleviate Hepatocyte Lipid Accumulation

Uncarboxylated Osteocalcin Decreases SCD1 by Activating AMPK to Alleviate Hepatocyte Lipid Accumulation

Caveolin-1 is involved in fatty infiltration and bone-tendon healing of rotator cuff tear

Zoledronate Promotes Peri-Implant Osteogenesis in Diabetic Osteoporosis by the AMPK Pathway

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