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High Concentration but Low Activity of Hepatocyte Growth Factor in Periodontitis
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden. PEAS Institute, Linköping, Sweden; Clinical Research Center, Örebro University, Örebro, Sweden.
Division of Cardiovascular Medicine, Department of Medical and Health Sciences, Linköping University, Linköping, Sweden; Centre for Oral Rehabilitation, Public Dental Health Care, County Council of Östergötland, Linköping, Sweden.
The Institution for Protein Environment Affinity Surveys (PEAS Institute), Linköping, Sweden.
Örebro University, School of Health and Medical Sciences, Örebro University, Sweden.
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2014 (English)In: Journal of Periodontology, ISSN 0022-3492, E-ISSN 1943-3670, Vol. 85, no 1, p. 113-122Article in journal (Refereed) Published
Abstract [en]

Background: High levels of hepatocyte growth factor (HGF), a healing factor with regenerative and cytoprotective effects, are associated with inflammatory diseases, including periodontitis. HGF biological activity requires binding to its receptors, the proto-oncogene c-Met (c-Met) and heparan sulphate proteoglycan (HSPG). Here we investigated HGF expression and its relationship to subgingival microbiota in medically healthy individuals with and without periodontitis.

Methods: Saliva, gingival crevicular fluid (GCF), and blood samples from 30 patients with severe periodontitis and 30 healthy controls were analyzed for HGF concentration using enzyme-linked immunosorbent assay (ELISA), and binding affinity for HSPG and c-Met using surface plasmon resonance (SPR). The regenerative effects of saliva from three patients and controls were analyzed in an in vitro model of cell injury. Subgingival plaques were analyzed for the presence of 18 bacterial species.

Results: Patients with periodontitis showed higher HGF concentrations in saliva, GCF, and serum (P < 0.001); however, the binding affinities for HSPG and c-Met were reduced in GCF and saliva (P < 0.002). In contrast to the controls, saliva from patients showed no significant regenerative effect over time on gingival epithelial cells. Compared to controls, patients had a higher prevalence of periodontal-related bacteria.

Conclusion: Higher circulatory HGF levels indicate a systemic effect of periodontitis. However, the HGF biological activity at local inflammation sites was reduced, and this effect was associated with the amount of periodontal bacteria. Loss of function of healing factors may be an important mechanism in degenerative processes in periodontally susceptible individuals.

Place, publisher, year, edition, pages
Chicago, USA: American Academy of Periodontology , 2014. Vol. 85, no 1, p. 113-122
Keywords [en]
Hepatocyte growth factor, porphyromonas gingivalis, periodontitis, systemic inflammation, coronary artery disease, chronic renal failure, lipoxin
National Category
Medical and Health Sciences Dentistry
Research subject
Biomedicine
Identifiers
URN: urn:nbn:se:oru:diva-29141DOI: 10.1902/jop.2013.130003ISI: 000331139400016PubMedID: 23594192Scopus ID: 2-s2.0-84890190195OAI: oai:DiVA.org:oru-29141DiVA, id: diva2:622698
Funder
Swedish Heart Lung FoundationSwedish Research Council
Note

Funding Agencies:

Public Dental Service in Ostergotland County, Sweden

Foundation of Olle Engkvist

Available from: 2013-05-23 Created: 2013-05-23 Last updated: 2018-06-04Bibliographically approved
In thesis
1. The role of peridontitis and hepatocyte growth factor in systemic inflammation
Open this publication in new window or tab >>The role of peridontitis and hepatocyte growth factor in systemic inflammation
2013 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

An essential goal in addressing inflammation is the return of tissue to homeostasis. Persistent infections often cause prolonged response and accumulation of immune cells, inducing imbalance in pro- and anti-inflammatory mediators, tissue destruction, and chronic inflammation. In periodontal disease, bacteria of the dental plaque are the primary aetiologic agents. Coronary artery disease (CAD) and chronic renal failure (CRF) are associated with periodontitis and involve systemic inflammation with atherosclerotic and fibrotic processes. The aims of this thesis were to study the effect of the bacterium Porphyromonas gingivalis and the anti-inflammatory mediator lipoxin A4 (LXA4) on blood cells in vitro, as well as to measure the expression of hepatocyte growth factor (HGF) in patients with periodontitis, CAD, and CRF. We found that LXA4 inhibits P. gingivalis–induced leukocyte platelet aggregation and reactive oxygen species (ROS) production in whole blood, by antagonizing the upregulation of CD11b/CD18 on leukocytes. The serum concentration of HGF was elevated in patients with periodontitis, CAD and CRF, indicating a systemic inflammation. However, the biological activity of HGF was reduced in serum from CRF patients and in saliva and gingival crevicular fluid of patients with periodontitis. This finding correlated with reduced growth of gingival epithelial cells incubated with saliva from patients with periodontitis. Neutrophil proteases reduced the biological activity of HGF in patients with CRF, and HGF expression in patients with periodontitis was associated with higher concentration and numbers of species of periodontal bacteria. In conclusion, these studies suggest that systemic spreading of periodontal bacteria, leukocyte-platelet activation and disturbed HGF-expression are crucial components involved in tissue degradation and progression of chronic inflammation.

Place, publisher, year, edition, pages
Örebro: Örebro universitet, 2013. p. 86
Series
Örebro Studies in Medicine, ISSN 1652-4063 ; 83
Keywords
Hepatocyte growth factor, Porphyromonas gingivalis, periodontitis, systemic inflammation, coronary artery disease, chronic renal failure, lipoxin
National Category
Medical and Health Sciences
Research subject
Biomedicine
Identifiers
urn:nbn:se:oru:diva-28541 (URN)978-91-7668-922-6 (ISBN)
Public defence
2013-05-08, 09:00 (Swedish)
Opponent
Supervisors
Available from: 2013-04-03 Created: 2013-04-03 Last updated: 2017-10-17Bibliographically approved

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