Porphyromonas gingivalis oral infection exacerbates the development and severity of collagen-induced arthritis

Julie Teresa Marchesan, Elizabeth Ann Gerow, Riley Schaff, Andrei Dan Taut, Seung Yun Shin, James Sugai, David Brand, Aaron Burberry, Julie Jorns, Steven Karl Lundy, Gabriel Nuñez, David A. Fox, William V. Giannobile

Research output: Contribution to journalArticle

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Abstract

Introduction: Clinical studies suggest a direct influence of periodontal disease (PD) on serum inflammatory markers and disease assessment of patients with established rheumatoid arthritis (RA). However, the influence of PD on arthritis development remains unclear. This investigation was undertaken to determine the contribution of chronic PD to immune activation and development of joint inflammation using the collagen-induced arthritis (CIA) model.Methods: DBA1/J mice orally infected with Porphyromonas gingivalis were administered with collagen II (CII) emulsified in complete Freund's adjuvant (CFA) or incomplete Freund's adjuvant (IFA) to induce arthritis. Arthritis development was assessed by visual scoring of paw swelling, caliper measurement of the paws, mRNA expression, paw micro-computed tomography (micro-CT) analysis, histology, and tartrate resistant acid phosphatase for osteoclast detection (TRAP)-positive immunohistochemistry. Serum and reactivated splenocytes were evaluated for cytokine expression.Results: Mice induced for PD and/or arthritis developed periodontal disease, shown by decreased alveolar bone and alteration of mRNA expression in gingival tissues and submandibular lymph nodes compared to vehicle. P. gingivalis oral infection increased paw swelling and osteoclast numbers in mice immunized with CFA/CII. Arthritis incidence and severity were increased by P. gingivalis in mice that received IFA/CII immunizations. Increased synovitis, bone erosions, and osteoclast numbers in the paws were observed following IFA/CII immunizations in mice infected with P gingivalis. Furthermore, cytokine analysis showed a trend toward increased serum Th17/Th1 ratios when P. gingivalis infection was present in mice receiving either CFA/CII or IFA/CII immunizations. Significant cytokine increases induced by P. gingivalis oral infection were mostly associated to Th17-related cytokines of reactivated splenic cells, including IL-1β, IL-6, and IL-22 in the CFA/CII group and IL-1β, tumor necrosis factor-α, transforming growth factor-β, IL-6 and IL-23 in the IFA/CII group.Conclusions: Chronic P. gingivalis oral infection prior to arthritis induction increases the immune system activation favoring Th17 cell responses, and ultimately accelerating arthritis development. These results suggest that chronic oral infection may influence RA development mainly through activation of Th17-related pathways.

Original languageEnglish (US)
Article numberR186
JournalArthritis Research and Therapy
Volume15
Issue number6
DOIs
StatePublished - Nov 12 2013

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Porphyromonas gingivalis
Experimental Arthritis
Collagen
Arthritis
Periodontal Diseases
Freund's Adjuvant
Infection
Osteoclasts
Cytokines
Immunization
Interleukin-1
Interleukin-6
Rheumatoid Arthritis
Interleukin-23
Th17 Cells
Bone and Bones
Messenger RNA
Synovitis
Transforming Growth Factors
Serum

All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Immunology and Allergy
  • Immunology

Cite this

Marchesan, J. T., Gerow, E. A., Schaff, R., Taut, A. D., Shin, S. Y., Sugai, J., ... Giannobile, W. V. (2013). Porphyromonas gingivalis oral infection exacerbates the development and severity of collagen-induced arthritis. Arthritis Research and Therapy, 15(6), [R186]. https://doi.org/10.1186/ar4376

Porphyromonas gingivalis oral infection exacerbates the development and severity of collagen-induced arthritis. / Marchesan, Julie Teresa; Gerow, Elizabeth Ann; Schaff, Riley; Taut, Andrei Dan; Shin, Seung Yun; Sugai, James; Brand, David; Burberry, Aaron; Jorns, Julie; Lundy, Steven Karl; Nuñez, Gabriel; Fox, David A.; Giannobile, William V.

In: Arthritis Research and Therapy, Vol. 15, No. 6, R186, 12.11.2013.

Research output: Contribution to journalArticle

Marchesan, JT, Gerow, EA, Schaff, R, Taut, AD, Shin, SY, Sugai, J, Brand, D, Burberry, A, Jorns, J, Lundy, SK, Nuñez, G, Fox, DA & Giannobile, WV 2013, 'Porphyromonas gingivalis oral infection exacerbates the development and severity of collagen-induced arthritis', Arthritis Research and Therapy, vol. 15, no. 6, R186. https://doi.org/10.1186/ar4376
Marchesan, Julie Teresa ; Gerow, Elizabeth Ann ; Schaff, Riley ; Taut, Andrei Dan ; Shin, Seung Yun ; Sugai, James ; Brand, David ; Burberry, Aaron ; Jorns, Julie ; Lundy, Steven Karl ; Nuñez, Gabriel ; Fox, David A. ; Giannobile, William V. / Porphyromonas gingivalis oral infection exacerbates the development and severity of collagen-induced arthritis. In: Arthritis Research and Therapy. 2013 ; Vol. 15, No. 6.
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abstract = "Introduction: Clinical studies suggest a direct influence of periodontal disease (PD) on serum inflammatory markers and disease assessment of patients with established rheumatoid arthritis (RA). However, the influence of PD on arthritis development remains unclear. This investigation was undertaken to determine the contribution of chronic PD to immune activation and development of joint inflammation using the collagen-induced arthritis (CIA) model.Methods: DBA1/J mice orally infected with Porphyromonas gingivalis were administered with collagen II (CII) emulsified in complete Freund's adjuvant (CFA) or incomplete Freund's adjuvant (IFA) to induce arthritis. Arthritis development was assessed by visual scoring of paw swelling, caliper measurement of the paws, mRNA expression, paw micro-computed tomography (micro-CT) analysis, histology, and tartrate resistant acid phosphatase for osteoclast detection (TRAP)-positive immunohistochemistry. Serum and reactivated splenocytes were evaluated for cytokine expression.Results: Mice induced for PD and/or arthritis developed periodontal disease, shown by decreased alveolar bone and alteration of mRNA expression in gingival tissues and submandibular lymph nodes compared to vehicle. P. gingivalis oral infection increased paw swelling and osteoclast numbers in mice immunized with CFA/CII. Arthritis incidence and severity were increased by P. gingivalis in mice that received IFA/CII immunizations. Increased synovitis, bone erosions, and osteoclast numbers in the paws were observed following IFA/CII immunizations in mice infected with P gingivalis. Furthermore, cytokine analysis showed a trend toward increased serum Th17/Th1 ratios when P. gingivalis infection was present in mice receiving either CFA/CII or IFA/CII immunizations. Significant cytokine increases induced by P. gingivalis oral infection were mostly associated to Th17-related cytokines of reactivated splenic cells, including IL-1β, IL-6, and IL-22 in the CFA/CII group and IL-1β, tumor necrosis factor-α, transforming growth factor-β, IL-6 and IL-23 in the IFA/CII group.Conclusions: Chronic P. gingivalis oral infection prior to arthritis induction increases the immune system activation favoring Th17 cell responses, and ultimately accelerating arthritis development. These results suggest that chronic oral infection may influence RA development mainly through activation of Th17-related pathways.",
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AU - Gerow, Elizabeth Ann

AU - Schaff, Riley

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AU - Shin, Seung Yun

AU - Sugai, James

AU - Brand, David

AU - Burberry, Aaron

AU - Jorns, Julie

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AU - Giannobile, William V.

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N2 - Introduction: Clinical studies suggest a direct influence of periodontal disease (PD) on serum inflammatory markers and disease assessment of patients with established rheumatoid arthritis (RA). However, the influence of PD on arthritis development remains unclear. This investigation was undertaken to determine the contribution of chronic PD to immune activation and development of joint inflammation using the collagen-induced arthritis (CIA) model.Methods: DBA1/J mice orally infected with Porphyromonas gingivalis were administered with collagen II (CII) emulsified in complete Freund's adjuvant (CFA) or incomplete Freund's adjuvant (IFA) to induce arthritis. Arthritis development was assessed by visual scoring of paw swelling, caliper measurement of the paws, mRNA expression, paw micro-computed tomography (micro-CT) analysis, histology, and tartrate resistant acid phosphatase for osteoclast detection (TRAP)-positive immunohistochemistry. Serum and reactivated splenocytes were evaluated for cytokine expression.Results: Mice induced for PD and/or arthritis developed periodontal disease, shown by decreased alveolar bone and alteration of mRNA expression in gingival tissues and submandibular lymph nodes compared to vehicle. P. gingivalis oral infection increased paw swelling and osteoclast numbers in mice immunized with CFA/CII. Arthritis incidence and severity were increased by P. gingivalis in mice that received IFA/CII immunizations. Increased synovitis, bone erosions, and osteoclast numbers in the paws were observed following IFA/CII immunizations in mice infected with P gingivalis. Furthermore, cytokine analysis showed a trend toward increased serum Th17/Th1 ratios when P. gingivalis infection was present in mice receiving either CFA/CII or IFA/CII immunizations. Significant cytokine increases induced by P. gingivalis oral infection were mostly associated to Th17-related cytokines of reactivated splenic cells, including IL-1β, IL-6, and IL-22 in the CFA/CII group and IL-1β, tumor necrosis factor-α, transforming growth factor-β, IL-6 and IL-23 in the IFA/CII group.Conclusions: Chronic P. gingivalis oral infection prior to arthritis induction increases the immune system activation favoring Th17 cell responses, and ultimately accelerating arthritis development. These results suggest that chronic oral infection may influence RA development mainly through activation of Th17-related pathways.

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