Local administration of anti-hepatocyte growth factor-neutralizing antibody reverts naturally occurring periodontitis

Yamaguchi, Yoko; Ohshima, Mitsuhiro

doi:10.1016/j.job.2021.07.001

Cited by 2 publications

(5 citation statements)

References 36 publications

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“…[28][29][30] HGF increases with the progression of periodontitis; higher levels of HGF have been shown to be correlated with massive inflammatory cell infiltration in clinical and pre-clinical studies. 10 In our study, periodontal tissues of HGF-Tg mice showed fewer T cells in the early stage of experimental periodontitis. However, the number of T cells was higher in HGF-Tg than WT mice in late stage of periodontitis.…”

Section: Discussionsupporting

confidence: 51%

“…Additionally, it has been claimed that HGF can stimulate monocyte migration and then promote bone destruction via enhanced chemokine production, and blocking of HGF/c‐MET signaling was found to inhibit bone damage 28–30 . HGF increases with the progression of periodontitis; higher levels of HGF have been shown to be correlated with massive inflammatory cell infiltration in clinical and pre‐clinical studies 10 …”

Section: Discussionmentioning

confidence: 99%

“…8,9 In vivo and in vitro studies have shown that anti-HGF-neutralizing antibodies can ameliorate the severity of naturally occurring periodontitis in cynomolgus monkeys. 10 As such, HGF levels offer a potential target for the diagnosis and treatment of human periodontitis. 5 HGF is a multifunctional growth factor that plays an important role in the regeneration, repair, and healing of various organs and tissues.…”

Section: Introductionmentioning

confidence: 99%

“…In in vitro experimental model of periodontitis, HGF can promote collagen degradation and epithelial apical migration in periodontitis 8,9 . In vivo and in vitro studies have shown that anti‐HGF‐neutralizing antibodies can ameliorate the severity of naturally occurring periodontitis in cynomolgus monkeys 10 . As such, HGF levels offer a potential target for the diagnosis and treatment of human periodontitis 5 …”

Section: Introductionmentioning

confidence: 99%

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Hepatocyte growth factor is protective in early stage but bone‐destructive in late stage of experimental periodontitis

Zhao,

Liu,

et al. 2024

J of Periodontal Research

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Background and ObjectiveClinical studies found high levels of hepatocyte growth factor (HGF) expression in patients with periodontitis. Studies suggest that HGF plays an important role in periodontitis, is involved in inflammation, and modulates alveolar bone integrity in periodontitis. This study aims to investigate the effects and mechanisms of HGF in the progression of experimental periodontitis.MethodsWe used silk thread ligation to induce periodontitis in HGF‐overexpressing transgenic (HGF‐Tg) and wild‐type C57BL/6J mice. The effects of HGF overexpression on alveolar bone destruction were assessed by microcomputed tomography imaging at baseline and on days 7, 14, 21, and 28. We analyzed the cytokines (IL‐6 and TNF‐α) and lymphocytes in periodontitis tissues by enzyme‐linked immunosorbent assay and flow cytometry. The effects of HGF on alveolar bone destruction were further tested by quantifying the systemic bone metabolism markers CTXI and PINP and by RNA sequencing for the signaling pathways involved in bone destruction. Western blotting and immunohistochemistry were performed to further elucidate the involved signaling pathways.ResultsWe found that experimental periodontitis increased HGF production in periodontitis tissues; however, the effects of HGF overexpression were inconsistent with disease progression. In the early stage of periodontitis, periodontal inflammation and alveolar bone destruction were significantly lower in HGF‐Tg mice than in wild‐type mice. In the late stage, HGF‐Tg mice showed higher inflammatory responses and progressively aggravated bone destruction with continued stimulation of inflammation. We identified the IL‐17/RANKL/TRAF6 pathway as a signaling pathway involved in the HGF effects on the progression of periodontitis.ConclusionHGF plays divergent effects in the progression of experimental periodontitis and accelerates osteoclastic activity and bone destruction in the late stage of inflammation.

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Section: Discussionsupporting

confidence: 51%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Hepatocyte growth factor is protective in early stage but bone‐destructive in late stage of experimental periodontitis

Zhao,

Liu,

et al. 2024

J of Periodontal Research

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“…Caspase‐8 is important in both cell death and inflammation and had previously been associated with the severity of periodontal conditions (Aral et al, 2019). Hepatocyte growth factor (HGF) is a well‐documented multi‐functional protein secreted by mesenchymal cells, activated epithelial cells and endothelial cells, among other cell types, and regulates mitogenesis, morphogenesis, cell proliferation, angiogenesis, cell motility and matrix invasion (Yamaguchi & Ohshima, 2021). HGF levels correlate with the severity of periodontitis (Yamaguchi & Ohshima, 2021) and BOP (Esberg et al, 2021), linking HGF both experimentally and clinically to periodontitis disease.…”

Section: Discussionmentioning

confidence: 99%

LIGHT protein: A novel gingival crevicular fluid biomarker associated with increased probing depth after periodontal surgery

Esberg,

Kindstedt,

Isehed

et al. 2024

J Clinic Periodontology

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AimTo evaluate the protein profiles in gingival crevicular fluid (GCF) in relation to clinical outcomes after periodontal surgery and examine if any selected proteins affect the mRNA expression of pro‐inflammatory cytokines in human gingival fibroblasts.Materials and MethodsThis exploratory study included 21 consecutive patients with periodontitis. GCF was collected, and the protein pattern (n = 92) and clinical parameters were evaluated prior to surgery and 3, 6 and 12 months after surgery. Fibroblastic gene expression was analysed by real‐time quantitative polymerase chain reaction.ResultsSurgical treatment reduced periodontal pocket depth (PPD) and changed the GCF protein pattern. Twelve months after surgery, 17% of the pockets showed an increase in PPD. Levels of a number of proteins in the GCF decreased after surgical treatment but increased with early signs of tissue destruction, with LIGHT being one of the proteins that showed the strongest association. Furthermore, LIGHT up‐regulated the mRNA expression of pro‐inflammatory cytokines interleukin (IL)‐6, IL‐8 and MMP9 in human gingival fibroblasts.ConclusionsLIGHT can potentially detect subjects at high risk of periodontitis recurrence after surgical treatment. Moreover, LIGHT induces the expression of inflammatory cytokines and tissue‐degrading enzymes in gingival fibroblasts.

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Local administration of anti-hepatocyte growth factor-neutralizing antibody reverts naturally occurring periodontitis

Cited by 2 publications

References 36 publications

Hepatocyte growth factor is protective in early stage but bone‐destructive in late stage of experimental periodontitis

Hepatocyte growth factor is protective in early stage but bone‐destructive in late stage of experimental periodontitis

LIGHT protein: A novel gingival crevicular fluid biomarker associated with increased probing depth after periodontal surgery

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