Effects by periodontitis on pristane-induced arthritis in rats.
An infection-immune association of periodontal disease with rheumatoid arthritis has been suggested. This study aimed to investigate the effect of pre-existing periodontitis on the development and the immune/inflammatory response of pristane-induced arthritis.



We investigated the effect of periodontitis induced by ligature placement and Porphyromonas gingivalis (P. gingivalis) infection, in combination with Fusobacterium nucleatum to promote its colonization, on the development of pristane-induced arthritis (PIA) in rats (Dark Agouti). Disease progression and severity of periodontitis and arthritis was monitored using clinical assessment, micro-computed tomography (micro-CT)/intraoral radiographs, antibody response, the inflammatory markers such as α-1-acid glycoprotein (α-1-AGP) and c-reactive protein (CRP) as well as cytokine multiplex profiling at different time intervals after induction.



Experimentally induced periodontitis manifested clinically (P < 0.05) prior to pristane injection and progressed steadily until the end of experiments (15 weeks), as compared to the non-ligated arthritis group. Injection of pristane 8 weeks after periodontitis-induction led to severe arthritis in all rats demonstrating that the severity of arthritis was not affected by the pre-existence of periodontitis. Endpoint analysis showed that 89% of the periodontitis-affected animals were positive for antibodies against arginine gingipain B and furthermore, the plasma antibody levels to a citrullinated P. gingivalis peptidylarginine deiminase (PPAD) peptide (denoted CPP3) were significantly (P < 0.05) higher in periodontitis rats with PIA. Additionally, there was a trend towards increased pro-inflammatory and anti-inflammatory cytokine levels, and increased α-1-AGP levels in plasma from periodontitis-challenged PIA rats.



Pre-existence of periodontitis induced antibodies against citrullinated peptide derived from PPAD in rats with PIA. However, there were no differences in the development or severity of PIA between periodontitis challenged and periodontitis free rats.
Division of Periodontology, Department of Dental Medicine, Karolinska Institutet, Box 4064, 141 04, Huddinge, Sweden. Kaja.Eriksson@ki.se.
Kaja
0000-0002-9490-8540
K
Eriksson
Section for Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77, Stockholm, Sweden.
Erik
E
Lönnblom
Division of Periodontology, Department of Dental Medicine, Karolinska Institutet, Box 4064, 141 04, Huddinge, Sweden.|Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital, Alfred Nobels Allé 8, 141 83, Huddinge, Sweden.
Gregory
G
Tour
Division of Periodontology, Department of Dental Medicine, Karolinska Institutet, Box 4064, 141 04, Huddinge, Sweden.
Anna
A
Kats
Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, The Laboratory Building, 5th Floor, 5021, Bergen, Norway.
Piotr
P
Mydel
Division of Periodontology, Department of Dental Medicine, Karolinska Institutet, Box 4064, 141 04, Huddinge, Sweden.
Pierre
P
Georgsson
Department of Laboratory Medicine, Karolinska Institutet at Karolinska University Hospital, Alfred Nobels Allé 8, 141 83, Huddinge, Sweden.
Catharina
C
Hultgren
Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Solna, Rheumatology Clinic D2:01, 171 76, Stockholm, Sweden.
Nastya
N
Kharlamova
Section for Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77, Stockholm, Sweden.
Ulrika
U
Norin
Division of Periodontology, Department of Dental Medicine, Karolinska Institutet, Box 4064, 141 04, Huddinge, Sweden.
Jörgen
J
Jönsson
Division of Periodontology, Department of Dental Medicine, Karolinska Institutet, Box 4064, 141 04, Huddinge, Sweden.
Anna
A
Lundmark
Broegelmann Research Laboratory, Department of Clinical Science, University of Bergen, The Laboratory Building, 5th Floor, 5021, Bergen, Norway.|Malopolska Centre of Biotechnology, Jagiellonian University, Gronostajowa 7a, 30-387, Kraków, Poland.
Annelie
A
Hellvard
Rheumatology Unit, Department of Medicine, Karolinska University Hospital, Solna, Rheumatology Clinic D2:01, 171 76, Stockholm, Sweden.
Karin
K
Lundberg
Division of Periodontology, Department of Dental Medicine, Karolinska Institutet, Box 4064, 141 04, Huddinge, Sweden.|Department of Periodontology at Eastmaninstitutet, Stockholm County Council, Dalagatan 11, 113 24, Stockholm, Sweden.
Leif
L
Jansson
Section for Medical Inflammation Research, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, 171 77, Stockholm, Sweden.|Center for Medical Immunopharmacology Research, Southern Medical University, Guangzhou, China.
Rikard
R
Holmdahl
Division of Periodontology, Department of Dental Medicine, Karolinska Institutet, Box 4064, 141 04, Huddinge, Sweden. Tulay.Lindberg@ki.se.
Tülay
T
Yucel-Lindberg
D018829:Adhesins, Bacterial / Q000097:blood / Q000276:immunology; D000818:Animals; D000917:Antibody Formation / Q000276:immunology; D001169:Arthritis, Experimental / Q000150:complications* / Q000000981:diagnostic imaging; D001835:Body Weight; D002097:C-Reactive Protein / Q000378:metabolism; D018925:Chemokines / Q000378:metabolism; D003546:Cysteine Endopeptidases / Q000097:blood / Q000276:immunology; D000080867:Gingipain Cysteine Endopeptidases; D006867:Hydrolases / Q000097:blood / Q000276:immunology; D008297:Male; D009961:Orosomucoid / Q000378:metabolism; D010518:Periodontitis / Q000139:chemically induced* / Q000150:complications* / Q000000981:diagnostic imaging / Q000382:microbiology; D016966:Porphyromonas gingivalis / Q000502:physiology; D000080063:Protein-Arginine Deiminase Type 3; D051381:Rats; D013729:Terpenes; D055114:X-Ray Microtomography
D018829:Adhesins, Bacterial; D018925:Chemokines; D000080867:Gingipain Cysteine Endopeptidases; D009961:Orosomucoid; D013729:Terpenes; C009042:pristane; D002097:C-Reactive Protein; D006867:Hydrolases; D003546:Cysteine Endopeptidases; D000080063:Protein-Arginine Deiminase Type 3
Arginine gingipain; Citrullinated peptide; Cytokine; Inflammation; Peptidylarginine deiminase; Periodontitis; Porphyromonas gingivalis; Pristane-induced arthritis