High Glucose Concentrations Suppress the Proliferation of Human Periodontal Ligament Stem Cells and Their Differentiation Into Osteoblasts

Kato, Hirohito; Taguchi, Yoichiro; Tominaga, Kazuhiro; Kimura, Daisuke; Yamawaki, Isao; Noguchi, Masahiro; Yamauchi, Nobuhiro; Tamura, Isao; Tanaka, Akio; Umeda, Makoto

doi:10.1902/jop.2015.150474

Cited by 64 publications

(55 citation statements)

References 41 publications

(80 reference statements)

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“…Our results together with previous findings 29,[40][41][42] postulate that impaired proliferation and osteoblast differentiation of cells present in the periodontium contributes to diabetes-associated spontaneous destruction of alveolar bone, whereas this impairment is improved by p-CA.…”

Section: Discussionsupporting

confidence: 85%

“…Incubating hPLFs at high glucose concentration also suppressed their proliferation and osteoblastic differentiation . Our results together with previous findings postulate that impaired proliferation and osteoblast differentiation of cells present in the periodontium contributes to diabetes‐associated spontaneous destruction of alveolar bone, whereas this impairment is improved by p ‐CA.…”

Section: Discussionsupporting

confidence: 82%

“…41 Incubating hPLFs at high glucose concentration also suppressed their proliferation and osteoblastic differentiation. 42 F I G U R E 6 The addition of p-coumaric acid (p-CA) improves impaired proliferation and osteoblast differentiation in human periodontal ligament fibroblasts (hPLFs) stimulated with high glucose concentration. A, hPLFs were incubated with the different concentrations of p-CA in presence of high glucose concentration (30 mmol/L) for 24 h, and then, viability of the cells was determined using a Cell Counting Kit (n = 5/group).…”

Section: Discussionmentioning

confidence: 99%

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Oral supplementation with p‐coumaric acid protects mice against diabetes‐associated spontaneous destruction of periodontal tissue

Bhattarai

Min

Jeon

et al. 2019

J of Periodontal Research

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Objective Dietary bioactive materials having anti‐inflammatory and antioxidant potentials are able to inhibit diabetes‐associated periodontal complications. Although numerous studies indicate that administration of p‐coumaric acid (p‐CA) ameliorates diabetes and diabetes‐related complications, the roles of p‐CA on periodontal tissue destruction in diabetic mice and the possible mechanisms therein are not completely understood. In this study, we evaluated whether supplementation with p‐CA protects mice against diabetes‐associated spontaneous periodontal destruction and also explored the associated mechanism therein using in vivo and in vitro experimental systems. Materials and Methods C57BL/6 male mice were divided into sham, streptozotocin (STZ), and STZ+CA groups (n = 5/group). Sham group was intraperitoneally injected with sodium buffer, whereas other two groups were injected with the buffer containing 160 mg/kg of STZ. STZ‐induced diabetic mice received oral gavage with p‐CA (50 mg/kg) (STZ+CA group) or with buffer only (STZ group) daily for 6 weeks. The effect of p‐CA on diabetes‐associated spontaneous periodontal destruction was evaluated using μCT analysis, hematoxylin and eosin staining, tartrate‐resistant acid phosphatase staining, and immunohistochemical staining methods. The efficacies of p‐CA on cell proliferation, osteoblast differentiation, reactive oxygen species (ROS) accumulation, and antioxidant‐related marker expression were examined using human periodontal ligament fibroblasts (hPLFs) cultured under high glucose condition. Results Streptozotocin group exhibited periodontal tissue destruction along with increased inflammation, oxidative stress, and osteoclast formation, as well as with decreased osteogenesis. However, oral administration with p‐CA protected mice against STZ‐induced periodontal destruction by inhibiting inflammation and osteoclastic activation. STZ+CA group also showed higher expression of antioxidant and osteogenic markers in periodontal tissue than did STZ group. Treatment with high glucose concentration (30 mmol/L) impaired proliferation and osteoblast differentiation of hPLFs along with cellular ROS accumulation, whereas these impairments were almost completely disappeared by supplementation with p‐CA. Conclusion These findings demonstrate that supplementation with p‐CA inhibits diabetes‐associated spontaneous destruction of periodontal tissue by enhancing anti‐inflammatory, anti‐osteoclastogenic, and antioxidant defense systems in STZ‐treated mice.

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Section: Discussionsupporting

confidence: 85%

Section: Discussionsupporting

confidence: 82%

Section: Discussionmentioning

confidence: 99%

See 1 more Smart Citation

Oral supplementation with p‐coumaric acid protects mice against diabetes‐associated spontaneous destruction of periodontal tissue

Bhattarai

Min

Jeon

et al. 2019

J of Periodontal Research

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“…While ligamental fibroblasts have been shown to exhibit a lowered proliferation rate when cultured for one week in a high glucose condition25, studies concerning short-term tenocyte culture within a day suggested no change in both proliferation and apoptosis1826. Our results demonstrated that tenocytes maintained similar growth rates between groups up to 14 days.…”

Section: Discussionmentioning

confidence: 45%

High glucose alters tendon homeostasis through downregulation of the AMPK/Egr1 pathway

Wang

Chang

et al. 2017

Sci Rep

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Diabetes mellitus (DM) is associated with higher risk of tendinopathy, which reduces tolerance to exercise and functional activities and affects lifestyle and glycemic control. Expression of tendon-related genes and matrix metabolism in tenocytes are essential for maintaining physiological functions of tendon. However, the molecular mechanisms involved in diabetic tendinopathy remain unclear. We hypothesized that high glucose (HG) alters the characteristics of tenocyte. Using in vitro 2-week culture of tenocytes, we found that expression of tendon-related genes, including Egr1, Mkx, TGF-β1, Col1a2, and Bgn, was significantly decreased in HG culture and that higher glucose consumption occurred. Down-regulation of Egr1 by siRNA decreased Scx, Mkx, TGF-β1, Col1a1, Col1a2, and Bgn expression. Blocking AMPK activation with Compound C reduced the expression of Egr1, Scx, TGF-β1, Col1a1, Col1a2, and Bgn in the low glucose condition. In addition, histological examination of tendons from diabetic mice displayed larger interfibrillar space and uneven glycoprotein deposition. Thus, we concluded that high glucose alters tendon homeostasis through downregulation of the AMPK/Egr1 pathway and the expression of downstream tendon-related genes in tenocytes. The findings render a molecular basis of the mechanism of diabetic tendinopathy and may help develop preventive and therapeutic strategies for the pathology.

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“…The small size of nodules and perturbation of calcium deposition imply that the high glucose concentrations alter osteoblastic bone formation, which increase the volume of immature mineralization similar to that of calcium deposition evoked by the presence of LPS [29][30][31][32] . Therefore, the only condition of high glucose concentration or stimulation by the P. gingivalis LPS is increased mineralization, but in both conditions, the mineralization had decreased.…”

Section: Discussionmentioning

confidence: 99%

Osteogenic Effects of Glucose Concentration for Human Bone Marrow Stromal Cells after Stimulation with <i>Porphyromonas gingivalis</i> Lipopolysaccharide

Shiomi

Yamawaki

Taguchi

et al. 2020

J. Hard Tissue Biology.

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Abstruct: Diabetes mellitus (DM) is a common disease occurring worldwide. Patients with DM are at an increased risk of losing their teeth compared to other individuals. DM increases the risk and severity of chronic inflammatory periodontal diseases, in which, bone resorption is found to occur. Chronic inflammation contributes to the development of DM and DM-associated complications. Hyperglycemia is a hallmark of DM and may contribute to sustained inflammation by increasing the levels of proinflammatory cytokines. However, the mechanisms by which bone-related complications develop in DM after stimulation by the Porphyromonas gingivalis lipopolysaccharide (P. gingivalis LPS) remain unknown. Results of studies performed to understand the effect of high glucose concentrations on the functions of osteoblasts are contradictory because some have suggested a subsequent increase (although others have suggested a decrease) in the rate of the biomineralization process. Therefore, we evaluated the effect of high glucose levels on the biomineralization and inflammation markers in a human osteoblastic cell line, after stimulation with LPS from P. gingivalis. We treated cells with glucose at concentrations 5.5, 8.0, 12 and 24 mM after stimulation with P. gingivalis LPS (1.0 mg/ml) and determined its effects on cell proliferation, alkaline phosphatase (ALP) activity, osteocalcin (OCN) production, calcium deposition, inflammatory cytokines, and osteogenic cytokines. Results demonstrated that high concentrations of glucose increased cell proliferation, but the ALP activity decreased at concentrations of 12 and 24 mM. Additionally, OCN production and Calcium (Ca) deposition decreased at 24 mM. The levels of inflammatory cytokines (IL-1β, IL-6 and IL-8) decreased at 8.0 and 12 mM. However, the amounts of Runx2 increased significantly in the presence of 12 mM glucose, but decreased beyond this concentration. High glucose concentration decreased hard tissue formation after stimulation by P. gingivalis LPS. Understanding the effect of glucose on osteoblast differentiation and calcium deposition might provide a better understanding of the development and prevention of periodontitis associated with diabetes.

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High Glucose Concentrations Suppress the Proliferation of Human Periodontal Ligament Stem Cells and Their Differentiation Into Osteoblasts

Abstract: The results of this study demonstrate that hyperglycemia inhibits human PDLSC proliferation and osteoblastic differentiation.

Cited by 64 publications

References 41 publications

Oral supplementation with p‐coumaric acid protects mice against diabetes‐associated spontaneous destruction of periodontal tissue

Oral supplementation with p‐coumaric acid protects mice against diabetes‐associated spontaneous destruction of periodontal tissue

High glucose alters tendon homeostasis through downregulation of the AMPK/Egr1 pathway

Osteogenic Effects of Glucose Concentration for Human Bone Marrow Stromal Cells after Stimulation with <i>Porphyromonas gingivalis</i> Lipopolysaccharide

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