Incretin accelerates platelet-derived growth factor-BB-induced osteoblast migration via protein kinase A: The upregulation of p38 MAP kinase

Kawabata, Tetsu; Tokuda, Harukuni; Kuroyanagi, Gen; Fujita, Kazuo; Sakai, Go; Kim, Woo; Matsushima‐Nishiwaki, Rie; Iida, Hiroki; Yata, Kenichiro; Wang, Shujie; Mizoguchi, Akira; Otsuka, Takanobu; Kozawa, Osamu

doi:10.1038/s41598-020-59392-7

Cited by 6 publications

(3 citation statements)

References 41 publications

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“…The scratch assay revealed a significant enhancement in the migration of MC3T3-E1 cells following P-GM-2 treatment (Figure J–K). Similar to the findings of this study, previous study has demonstrated that incretins facilitate bone repair by expediting the migration of osteoblasts . The findings suggested that P-GM-2 significantly enhanced the growth, differentiation, and mineralization of osteoblasts, implying its potential role in regulating bone formation through osteogenic activity.…”

Section: Resultssupporting

confidence: 90%

Novel Peptide Derived from Gadus morhua Stimulates Osteoblastic Differentiation and Mineralization through Wnt/β-Catenin and BMP Signaling Pathways

Yang,

Gao,

Cheng

et al. 2024

J. Agric. Food Chem.

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Marine biodiversity offers a wide array of active ingredient resources. Gadus morhua peptides (GMPs) showed excellent osteoprotective effects in ovariectomized mice. However, the potential osteogenesis mechanisms of key osteogenic peptides in GMP were seldom reported. In this study, a novel osteogenic peptide (GETNPADSKPGSIR, P-GM-2) was screened from GMP. P-GM-2 has a high stability coefficient and a strong interaction with epidermal growth factor receptor. Cell culture experiments showed that P-GM-2 stimulated the expression of osteogenic differentiation markers to promote osteoblast proliferation, differentiation, and mineralization. Additionally, P-GM-2 phosphorylates GSK-3β, leading to the stabilization of β-catenin and its translocation to the nucleus, thus initiating the activation of the Wnt/β-catenin signaling pathway. Meanwhile, P-GM-2 could also regulate the osteogenic differentiation of preosteoblasts by triggering the BMP/Smad and mitogen-activated protein kinase signaling pathways. Further validation with specific inhibitors (ICG001 and Noggin) demonstrated that the osteogenic activity of P-GM-2 was revealed by the activation of the BMP and Wnt/β-catenin pathways. In summary, these results provide theoretical and practical insights into P-GM-2 as an effective antiosteoporosis active ingredient.

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Section: Resultssupporting

confidence: 90%

Novel Peptide Derived from Gadus morhua Stimulates Osteoblastic Differentiation and Mineralization through Wnt/β-Catenin and BMP Signaling Pathways

Yang,

Gao,

Cheng

et al. 2024

J. Agric. Food Chem.

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“…Also, PI3K and MAPK were requisite in PDGF-BB-mediated MSC motility toward glioma [ 26 ]. Previous studies on osteogenic MC3T3-E1 cells showed that the mitogenic response stimulated by PDGF-BB was dependent on extracellular signal-regulated kinase (Erk) and JNK, whereas the migratory response involved MAPK and JNK [ 27 ]. JNK was further verified with significance in PDGF-induced proliferation and migration of MSCs [ 28 ].…”

Section: Discussionmentioning

confidence: 99%

Endothelial Cells Promote Migration of Mesenchymal Stem Cells via PDGF-BB/PDGFRβ-Src-Akt in the Context of Inflammatory Microenvironment upon Bone Defect

Hou

Zhou

et al. 2022

Stem Cells International

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Homing of mesenchymal stem cells (MSCs) to the defect site is indispensable for bone repair. Local endothelial cells (ECs) can recruit MSCs; however, the mechanism remains unclear, especially in the context of the inflammatory microenvironment. This study was aimed to investigate the role of ECs in MSCs migration during the inflammatory phase of bone repair. The inflammatory microenvironment was mimicked in vitro via adding a cytokine set (IL-1β, IL-6, and TNF-α) to the culture medium of ECs. The production of PDGF-BB from ECs was measured by ELISA. Transwell and wound healing assays were employed to assess MSCs migration toward ECs and evaluate the implication of PDGF-BB/PDGFRβ. A series of shRNA and pathway inhibitors were used to screen signal molecules downstream of PDGF-BB/PDGFRβ. Then, mouse models of femoral defects were fabricated and DBM scaffolds were implanted. GFP+ MSCs were injected via tail vein, and the relevance of PDGF-BB/PDGFRβ, as well as screened signal molecules, in cell homing was further verified during the early phase of bone repair. In the mimicked inflammatory microenvironment, MSCs migration toward ECs was significantly promoted, which could be abrogated by pdgfrb knockout in MSCs. Inhibition of Src or Akt led to negative effects analogous to pdgfrb knockout. Blockade of JNK, MEK, and p38 MAPK had no impact. Meanwhile, the secretion of PDGF-BB from ECs was evidently motivated by the inflammatory microenvironment. Adding recombinant PDGF-BB protein to the culture medium of ECs phenocopied the inflammatory microenvironment with regard to attracting MSCs, which was abolished by pdgfb, src, or akt in MSCs. Moreover, pdgfb knockout suppressed the expression and phosphorylation of Src and Akt in migrating MSCs. Src knockout impaired Akt expression but not vice versa. In vivo, reduced infiltration of CD31+ ECs was correlated with diminished PDGF-BB in local defect sites, and silencing pdgfb, src, or akt in MSCs markedly hampered cell homing. Together, these findings suggest that in the inflammatory microenvironment, MSCs migrate toward ECs via PDGF-BB/PDGFRβ and the downstream Src-Akt signal pathway.

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“…Under physiological conditions, DPP‐IV is a protease that cleaves dipeptides specifically from proteins and oligopeptides after the penultimate N‐terminal cleavage of proline or alanine 37 . DPP‐IV is involved in the degradation of a number of neuropeptides, peptide hormones, and cytokines, including incretins GLP‐1 and GIPs 38 . When glucose is ingested, GLP‐1 and GIPs are rapidly degraded by DPP‐IV.…”

Section: Discussionmentioning

confidence: 99%

Efficacy and safety of DPP‐IV inhibitors combined with basal insulin in the treatment of type 2 diabetes

Pan¹,

Yang

Zhang

2020

Journal of Diabetes

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Background To evaluate the efficacy and safety of dipeptidyl peptidase IV (DPP‐IV) inhibitors when added to insulin therapy in patients with type 2 diabetes mellitus (T2DM). Methods PubMed, EMBASE, the Web of Science, and the Cochrane Library were systematically searched for randomized controlled trials (RCTs) exploring the efficacy or safety of DPP‐IV inhibitors in T2DM patients. The quality of the included RCTs was assessed with the Cochrane risk‐of‐bias tool. For outcomes, odds ratios or weighted mean differences (WMDs) with 95% CIs were calculated using both random‐ and fixed‐effects models. Results A total of 16 studies were included in the meta‐analysis with 5418 participants. Glycosylated hemoglobin (HbA1c) was significantly decreased in the DPP‐IV inhibitors with insulin (DPP‐IVi/INS) group compared with the insulin‐alone (with or without placebo) group (WMD = −0.62%; 95% CI: −0.74, −0.49; P < .05). Consistent with this finding, the fasting blood glucose (FBG)‐lowering effect (WMD = −0.61 mmol/L; 95% CI: −0.77, −0.45; P < .05) and 2‐hour postprandial glucose (2hPPG)‐lowering efficacy (WMD = −2.39 mmol/L; 95% CI: −2.81, −1.97; P < .05) in the DPP‐IVi/INS group were also significantly better than in the insulin‐alone group. Regarding safety indicators, compared with the insulin‐alone group, DPP‐IVi/INS treatments had no association with the risk of adverse effects, including hypoglycemia, adverse events (AEs), and serious adverse events (SAEs). Conclusions Compared with insulin treatment alone, treatment with DPP‐IVi/INS improved HbA1c, FBG, and 2hPPG without increasing the risk of hypoglycemia, AEs, or SAEs.

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Incretin accelerates platelet-derived growth factor-BB-induced osteoblast migration via protein kinase A: The upregulation of p38 MAP kinase

Cited by 6 publications

References 41 publications

Novel Peptide Derived from Gadus morhua Stimulates Osteoblastic Differentiation and Mineralization through Wnt/β-Catenin and BMP Signaling Pathways

Novel Peptide Derived from Gadus morhua Stimulates Osteoblastic Differentiation and Mineralization through Wnt/β-Catenin and BMP Signaling Pathways

Endothelial Cells Promote Migration of Mesenchymal Stem Cells via PDGF-BB/PDGFRβ-Src-Akt in the Context of Inflammatory Microenvironment upon Bone Defect

Efficacy and safety of DPP‐IV inhibitors combined with basal insulin in the treatment of type 2 diabetes

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