Ghrelin accelerates the cartilagic differentiation of rabbit mesenchymal stem cells through the ERK1/2 pathway

Ye, Nan; Wang, Lin; Dou, Zhe; Huang, Jian

doi:10.1007/s10616-017-0156-6

Cited by 9 publications

(4 citation statements)

References 25 publications

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“…Some researchers believed that ghrelin confers its function through modulation of growth hormone level, energy balance, cardiovascular cells' fate, and autonomic nervous activity [8,31]. Also, current experimental evidence suggests that ghrelin may media various signaling pathways, including PI3K/AKT [30], mTOR [29], ERK1/2 [32], AMPK, NF-jB [33], and MAPK [34] pathways. Among which, PI3K/AKT has been widely accepted as key signaling in the protection of myocardial ischemia-reperfusion injury [35,36].…”

Section: Discussionmentioning

confidence: 99%

Pretreatment of ghrelin protects H9c2 cells against hypoxia/reoxygenation-induced cell death via PI3K/AKT and AMPK pathways

Chen

Wang

Zhang

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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Ghrelin has been widely recognized as a key peptide in the cardiovascular system. This study detected the potential of ghrelin in MI management and tried to decode one of the possible underlying mechanisms. H9c2 cells were pretreated with ghrelin and were subjected to hypoxia/reoxygenation (H/R). CCK-8, flow cytometry, Western blot and LDH analysis were conducted to assess the changes in cell survival. LY294002 and Compound C were used to treat H9c2 cells for blocking PI3K/AKT and AMPK pathways, respectively. Ghrelin expression in H9c2 cells was suppressed by siRNA-mediated silencing to see the effects of endogenous ghrelin. We found that, following H/R, H9c2 cells viability was decreased, CyclinD1 and CDK4 were down-regulated, apoptosis was induced, the release of LDH was enhanced, and the expression levels of Cox-2 and iNOS were up-regulated. Ghrelin protected H9c2 cells against H/R induced these alterations. Besides, ghrelin activated PI3K/AKT and AMPK pathways even in H/Rstimulated cells. The protective effects of ghrelin against H/R-induced cell damage were all attenuated by the addition of LY294002 or Compound C. Moreover, endogenous inhibition of ghrelin significantly induced cell death of H9c2 cells. In conclusion, this study demonstrated that ghrelin pretreatment protected H9c2 cells against H/R-induced cell damage, possibly via PI3K/AKT and AMPK pathways. ARTICLE HISTORY

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Section: Discussionmentioning

confidence: 99%

Pretreatment of ghrelin protects H9c2 cells against hypoxia/reoxygenation-induced cell death via PI3K/AKT and AMPK pathways

Chen

Wang

Zhang

et al. 2019

Artificial Cells, Nanomedicine, and Biotechnology

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“…The expression of ghrelin was observed to be localized primarily in the epiphyseal growth plates' proliferative and maturative zone in both rat and human cartilage , which further supports the hypothesis that ghrelin could act as a growth factor for chondrocytes. Ye et al also found that ghrelin could induce differentiation of rabbit mesenchymal stem cells into cartilage through induction of the extracellular regulated protein kinases 1/2 pathway . In recent studies, ghrelin has been proven to prevent OA.…”

Section: Introductionmentioning

confidence: 96%

Attenuated levels of ghrelin in synovial fluid is related to the disease severity of ankle post‐traumatic osteoarthritis

Zou

Yang³

et al. 2019

BioFactors

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Post‐traumatic osteoarthritis (PTOA) of ankle joints results in pain and reduced joint function. Ghrelin, a 28‐amino‐acid polypeptide, has been previously identified as the first cognate natural ligand that binds to the growth hormone secretagogue receptor. In the present study, ghrelin has been validated to exert cartilage‐protective and anti‐inflammatory effects. The current study was aimed at investigating the potential role of the levels of serum and synovial fluid (SF) ghrelin on the severity of disease in patients suffering from ankle PTOA. Ninety‐seven patients with ankle osteoarthritis who received an arthroscopical examination and debridement or replacement of the ankle joint were included in the study cohort. Meanwhile, 95 healthy individuals (whose age and sex were matched) who received periodic body checkups were enrolled as healthy controls. Enzyme‐linked immunosorbent assay (ELISA) was used to analyze the ghrelin levels in serum and SF. SF was also probed for cartilage degradation enzyme matrix metalloproteinases‐3 (MMP‐3) and tumor necrosis factor alpha (TNF‐α), which is a known pro‐inflammatory cytokine. The clinical evaluation was carried out using the American Orthopedic Foot and Ankle Society (AOFAS) ankle‐hindfoot rating scale and visual analogue scale (VAS). The radiographic severity was evaluated using the modified Kellgren–Lawrence (K–L) grading system. We scored for the modified Mankin's score to depict histopathological changes due to cartilage lesions. The diagnostic relevance of the ghrelin concentrations in the prediction of the radiographic grading (in comparison with MMP‐3 and TNF‐α) was evaluated by calculating the area under the curve of the receiver operating characteristic (ROC) curve. The serum abundance of ghrelin was not significantly altered between ankle PTOA patients and healthy controls. SF ghrelin was negatively correlated with radiographic progression determined by modified ankle K–L grades. In addition SF ghrelin concentrations were negatively related to VAS scores, and positively associated with AOFAS ankle‐hindfoot rating. Moreover, SF ghrelin was inversely proportional to the expressions of MMP‐3 and TNF‐α. ROC analysis curve demonstrated that ghrelin serves as a favorable marker for the diagnosis of radiographic severity by modified ankle K‐L grade. The ghrelin concentration in SF is negatively proportional to disease progression in patients suffering from ankle PTOA. Local administration of ghrelin may function as a decent adjuvant therapy to delay the progress of ankle PTOA. © 2019 BioFactors, 45(3):463–470, 2019

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“…In previous studies (Ye and Jiang 2015;Ye et al 2018), we have shown that ghrelin triggers the osteogenic differentiation of rabbit bone marrowderived mesenchymal stromal cells (rMSCs) through the ERK1/2 signaling pathway; however, the function of miR-206 in this process has not been explored. Thus, in the present study, we investigated the function of miR-206 in the ghrelin-mediated osteogenic differentiation of rMSCs.…”

Section: Introductionmentioning

confidence: 99%

Ghrelin promotes the osteogenic differentiation of rMSCs via miR-206 and the ERK1/2 pathway

Yang

et al. 2020

Cytotechnology

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Objective Mesenchymal stem cells (MSCs) can differentiate into chondroblasts, adipocytes, or osteoblasts under appropriate stimulation. Ghrelin, an endogenous ligand for the growth hormone secretagogue receptor (GHSR), stimulates growth hormone (GH) secretion and exerts both orexigenic and adipogenic effects. The ERK1/2 signaling pathway is known to trigger osteogenic differentiation of rabbit bone marrow-derived mesenchymal stromal cells. In the present study, the function of miR-206 in the ghrelin-mediated osteogenic differentiation of rabbit bone marrow-derived mesenchymal stromal cells (rMSCs) was explored. Methods The expression of miR-206 was detected by qPCR, and phosphorylated ERK1/2 and the protein expression levels of ALP, RUNX2, and Osterix were assessed by western blotting. Results: Ghrelin inhibited the expression of miR-206 to promote the osteogenic differentiation of rMSCs. Moreover, ghrelin increased the phosphorylation of ERK1/2, while overexpression of miR-206 suppressed ERK1/2 phosphorylation, indicating that miR-206 can regulate the ERK1/2 pathway. Further, inhibition of ERK1/2 had no influence on miR-206 expression; however, the phosphorylation of ERK1/2 was decreased, and the protein expression levels of ALP, RUNX2, and Osterix were downregulated. Conclusions: Ghrelin promotes the osteogenic differentiation of rMSCs via miR-206 and the ERK1/2 pathway.

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Ghrelin accelerates the cartilagic differentiation of rabbit mesenchymal stem cells through the ERK1/2 pathway

Cited by 9 publications

References 25 publications

Pretreatment of ghrelin protects H9c2 cells against hypoxia/reoxygenation-induced cell death via PI3K/AKT and AMPK pathways

Pretreatment of ghrelin protects H9c2 cells against hypoxia/reoxygenation-induced cell death via PI3K/AKT and AMPK pathways

Attenuated levels of ghrelin in synovial fluid is related to the disease severity of ankle post‐traumatic osteoarthritis

Ghrelin promotes the osteogenic differentiation of rMSCs via miR-206 and the ERK1/2 pathway

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