Skip to main content
Top
Published in: Arthritis Research & Therapy 1/2015

Open Access 01-12-2015 | Research article

Trabecular bone loss in collagen antibody-induced arthritis

Authors: Louise Grahnemo, Annica Andersson, Merja Nurkkala-Karlsson, Alexandra Stubelius, Marie K. Lagerquist, Mattias N. D. Svensson, Claes Ohlsson, Hans Carlsten, Ulrika Islander

Published in: Arthritis Research & Therapy | Issue 1/2015

Login to get access

Abstract

Introduction

Postmenopausal women with rheumatoid arthritis (RA) have increased risk of developing osteoporosis due to chronic inflammation and estrogen deprivation. Collagen antibody-induced arthritis (CAIA), an experimental polyarthritis model representing the effector phase of arthritis, is mainly mediated by the innate immune system. Compared to the widely used collagen-induced arthritis model, CAIA is conveniently short and can be used in C57BL/6 mice, enabling studies with knock-out mice. However, the impact on bone of the CAIA model in C57BL/6 mice has not previously been studied. Therefore, the aim of this study was to determine if CAIA can be used to study postmenopausal arthritis-induced osteoporosis.

Methods

CAIA was induced by administration of collagen-type II antibodies and lipopolysaccharide to ovariectomized female C57BL/6J mice. Control mice received lipopolysaccharide, but no antibodies. Nine days later, femurs were collected for high-resolution micro-CT and histomorphometry. Serum was used to assess cartilage breakdown and levels of complement. Frequencies of immune cell subsets from bone marrow and lymph nodes were analyzed by flow cytometery.

Results

Trabecular bone mass was decreased and associated with increased number of osteoclasts per bone surface in the CAIA model. Also, the frequency of interleukin-17+ cells in lymph nodes was increased in CAIA.

Conclusion

The present study show that CAIA, a short reproducible arthritis model that is compatible with C57BL/6 mice, is associated with increased number of osteoclasts and trabecular bone loss.
Literature
1.
go back to reference Forsblad D’Elia H, Larsen A, Waltbrand E, Kvist G, Mellstrom D, Saxne T, et al. Radiographic joint destruction in postmenopausal rheumatoid arthritis is strongly associated with generalised osteoporosis. Ann Rheum Dis. 2003;62:617–23.PubMedCrossRef Forsblad D’Elia H, Larsen A, Waltbrand E, Kvist G, Mellstrom D, Saxne T, et al. Radiographic joint destruction in postmenopausal rheumatoid arthritis is strongly associated with generalised osteoporosis. Ann Rheum Dis. 2003;62:617–23.PubMedCrossRef
2.
go back to reference Kvien TK, Uhlig T, Ødegård S, Heiberg MS. Epidemiological aspects of rheumatoid arthritis. Ann N Y Acad Sci. 2006;1069:212–22.PubMedCrossRef Kvien TK, Uhlig T, Ødegård S, Heiberg MS. Epidemiological aspects of rheumatoid arthritis. Ann N Y Acad Sci. 2006;1069:212–22.PubMedCrossRef
3.
go back to reference Goemaere S, Ackerman C, Goethals K, De Keyser F, Van der Straeten C, Verbruggen G, et al. Onset of symptoms of rheumatoid arthritis in relation to age, sex and menopausal transition. J Rheumatol. 1990;17:1620–2.PubMed Goemaere S, Ackerman C, Goethals K, De Keyser F, Van der Straeten C, Verbruggen G, et al. Onset of symptoms of rheumatoid arthritis in relation to age, sex and menopausal transition. J Rheumatol. 1990;17:1620–2.PubMed
4.
go back to reference Jochems C, Islander U, Erlandsson M, Verdrengh M, Ohlsson C, Carlsten H. Osteoporosis in experimental postmenopausal polyarthritis: the relative contributions of estrogen deficiency and inflammation. Arthritis Res Ther. 2005;7:R837–43.PubMedCentralPubMedCrossRef Jochems C, Islander U, Erlandsson M, Verdrengh M, Ohlsson C, Carlsten H. Osteoporosis in experimental postmenopausal polyarthritis: the relative contributions of estrogen deficiency and inflammation. Arthritis Res Ther. 2005;7:R837–43.PubMedCentralPubMedCrossRef
5.
go back to reference Marenzana M, Vugler A, Moore A, Robinson M. Effect of sclerostin-neutralising antibody on periarticular and systemic bone in a murine model of rheumatoid arthritis: a microCT study. Arthritis Res Ther. 2013;15:R125.PubMedCentralPubMedCrossRef Marenzana M, Vugler A, Moore A, Robinson M. Effect of sclerostin-neutralising antibody on periarticular and systemic bone in a murine model of rheumatoid arthritis: a microCT study. Arthritis Res Ther. 2013;15:R125.PubMedCentralPubMedCrossRef
6.
go back to reference Saidenberg-Kermanac’h N, Corrado A, Lemeiter D, deVernejoul MC, Boissier MC, Cohen-Solal ME. TNF-alpha antibodies and osteoprotegerin decrease systemic bone loss associated with inflammation through distinct mechanisms in collagen-induced arthritis. Bone. 2004;35:1200–7.PubMedCrossRef Saidenberg-Kermanac’h N, Corrado A, Lemeiter D, deVernejoul MC, Boissier MC, Cohen-Solal ME. TNF-alpha antibodies and osteoprotegerin decrease systemic bone loss associated with inflammation through distinct mechanisms in collagen-induced arthritis. Bone. 2004;35:1200–7.PubMedCrossRef
7.
go back to reference Nandakumar KS, Svensson L, Holmdahl R. Collagen type II-specific monoclonal antibody-induced arthritis in mice: description of the disease and the influence of age, sex, and genes. Am J Pathol. 2003;163:1827–37.PubMedCentralPubMedCrossRef Nandakumar KS, Svensson L, Holmdahl R. Collagen type II-specific monoclonal antibody-induced arthritis in mice: description of the disease and the influence of age, sex, and genes. Am J Pathol. 2003;163:1827–37.PubMedCentralPubMedCrossRef
8.
go back to reference Terato K, Hasty KA, Reife RA, Cremer MA, Kang AH, Stuart JM. Induction of arthritis with monoclonal antibodies to collagen. J Immunol. 1992;148:2103–8.PubMed Terato K, Hasty KA, Reife RA, Cremer MA, Kang AH, Stuart JM. Induction of arthritis with monoclonal antibodies to collagen. J Immunol. 1992;148:2103–8.PubMed
9.
go back to reference Nandakumar KS, Holmdahl R. Antibody-induced arthritis: disease mechanisms and genes involved at the effector phase of arthritis. Arthritis Res Ther. 2006;8:223.PubMedCentralPubMedCrossRef Nandakumar KS, Holmdahl R. Antibody-induced arthritis: disease mechanisms and genes involved at the effector phase of arthritis. Arthritis Res Ther. 2006;8:223.PubMedCentralPubMedCrossRef
10.
11.
go back to reference Cook AD, Rowley MJ, Mackay IR, Gough A, Emery P. Antibodies to type II collagen in early rheumatoid arthritis. Correlation with disease progression. Arthritis Rheum. 1996;39:1720–7.PubMedCrossRef Cook AD, Rowley MJ, Mackay IR, Gough A, Emery P. Antibodies to type II collagen in early rheumatoid arthritis. Correlation with disease progression. Arthritis Rheum. 1996;39:1720–7.PubMedCrossRef
12.
go back to reference Grahnemo L, Jochems C, Andersson A, Engdahl C, Ohlsson C, Islander U, et al. Possible role of lymphocytes in glucocorticoid-induced increase in trabecular bone mineral density. J Endocrinol. 2015;224:97–108.PubMedCentralPubMedCrossRef Grahnemo L, Jochems C, Andersson A, Engdahl C, Ohlsson C, Islander U, et al. Possible role of lymphocytes in glucocorticoid-induced increase in trabecular bone mineral density. J Endocrinol. 2015;224:97–108.PubMedCentralPubMedCrossRef
13.
go back to reference Toyosawa S, Ogawa Y, Chang CK, Hong SS, Yagi T, Kuwahara H, et al. Histochemistry of tartrate-resistant acid phosphatase and carbonic anhydrase isoenzyme II in osteoclast-like giant cells in bone tumours. Virchows Arch A Pathol Anat Histopathol. 1991;418:255–61.PubMedCrossRef Toyosawa S, Ogawa Y, Chang CK, Hong SS, Yagi T, Kuwahara H, et al. Histochemistry of tartrate-resistant acid phosphatase and carbonic anhydrase isoenzyme II in osteoclast-like giant cells in bone tumours. Virchows Arch A Pathol Anat Histopathol. 1991;418:255–61.PubMedCrossRef
14.
go back to reference Banda NK, Takahashi K, Wood AK, Holers VM, Arend WP. Pathogenic complement activation in collagen antibody-induced arthritis in mice requires amplification by the alternative pathway. J Immunol. 2007;179:4101–9.PubMedCrossRef Banda NK, Takahashi K, Wood AK, Holers VM, Arend WP. Pathogenic complement activation in collagen antibody-induced arthritis in mice requires amplification by the alternative pathway. J Immunol. 2007;179:4101–9.PubMedCrossRef
15.
go back to reference Okamoto K, Takayanagi H. Osteoclasts in arthritis and Th17 cell development. Int Immunopharmacol. 2011;11:543–8.PubMedCrossRef Okamoto K, Takayanagi H. Osteoclasts in arthritis and Th17 cell development. Int Immunopharmacol. 2011;11:543–8.PubMedCrossRef
16.
go back to reference Kobayashi K, Takahashi N, Jimi E, Udagawa N, Takami M, Kotake S, et al. Tumor necrosis factor alpha stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL-RANK interaction. J Exp Med. 2000;191:275–86.PubMedCentralPubMedCrossRef Kobayashi K, Takahashi N, Jimi E, Udagawa N, Takami M, Kotake S, et al. Tumor necrosis factor alpha stimulates osteoclast differentiation by a mechanism independent of the ODF/RANKL-RANK interaction. J Exp Med. 2000;191:275–86.PubMedCentralPubMedCrossRef
17.
go back to reference Kotake S, Udagawa N, Takahashi N, Matsuzaki K, Itoh K, Ishiyama S, et al. IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest. 1999;103:1345–52.PubMedCentralPubMedCrossRef Kotake S, Udagawa N, Takahashi N, Matsuzaki K, Itoh K, Ishiyama S, et al. IL-17 in synovial fluids from patients with rheumatoid arthritis is a potent stimulator of osteoclastogenesis. J Clin Invest. 1999;103:1345–52.PubMedCentralPubMedCrossRef
18.
go back to reference Katayama M, Ohmura K, Yukawa N, Terao C, Hashimoto M, Yoshifuji H, et al. Neutrophils are essential as a source of IL-17 in the effector phase of arthritis. PLoS One. 2013;8:e62231.PubMedCentralPubMedCrossRef Katayama M, Ohmura K, Yukawa N, Terao C, Hashimoto M, Yoshifuji H, et al. Neutrophils are essential as a source of IL-17 in the effector phase of arthritis. PLoS One. 2013;8:e62231.PubMedCentralPubMedCrossRef
19.
go back to reference Nandakumar KS, Backlund J, Vestberg M, Holmdahl R. Collagen type II (CII)-specific antibodies induce arthritis in the absence of T or B cells but the arthritis progression is enhanced by CII-reactive T cells. Arthritis Res Ther. 2004;6:R544–50.PubMedCentralPubMedCrossRef Nandakumar KS, Backlund J, Vestberg M, Holmdahl R. Collagen type II (CII)-specific antibodies induce arthritis in the absence of T or B cells but the arthritis progression is enhanced by CII-reactive T cells. Arthritis Res Ther. 2004;6:R544–50.PubMedCentralPubMedCrossRef
20.
go back to reference Hueber AJ, Asquith DL, Miller AM, Reilly J, Kerr S, Leipe J, et al. Mast cells express IL-17A in rheumatoid arthritis synovium. J Immunol. 2010;184:3336–40.PubMedCrossRef Hueber AJ, Asquith DL, Miller AM, Reilly J, Kerr S, Leipe J, et al. Mast cells express IL-17A in rheumatoid arthritis synovium. J Immunol. 2010;184:3336–40.PubMedCrossRef
22.
go back to reference Nichols WK. LPS stimulation of complement (C3) synthesis by a human monocyte cell line. Complement. 1984;1:108–15.PubMed Nichols WK. LPS stimulation of complement (C3) synthesis by a human monocyte cell line. Complement. 1984;1:108–15.PubMed
23.
go back to reference Jochems C, Islander U, Erlandsson M, Engdahl C, Lagerquist M, Ohlsson C, et al. Effects of oestradiol and raloxifene on the induction and effector phases of experimental postmenopausal arthritis and secondary osteoporosis. Clin Exp Immunol. 2011;165:121–9.PubMedCentralPubMedCrossRef Jochems C, Islander U, Erlandsson M, Engdahl C, Lagerquist M, Ohlsson C, et al. Effects of oestradiol and raloxifene on the induction and effector phases of experimental postmenopausal arthritis and secondary osteoporosis. Clin Exp Immunol. 2011;165:121–9.PubMedCentralPubMedCrossRef
24.
go back to reference Perilli E, Cantley M, Marino V, Crotti TN, Smith MD, Haynes DR, et al. Quantifying not only bone loss, but also soft tissue swelling, in a murine inflammatory arthritis model using micro-computed tomography. Scand J Immunol. 2015;81:142–50.PubMedCentralPubMedCrossRef Perilli E, Cantley M, Marino V, Crotti TN, Smith MD, Haynes DR, et al. Quantifying not only bone loss, but also soft tissue swelling, in a murine inflammatory arthritis model using micro-computed tomography. Scand J Immunol. 2015;81:142–50.PubMedCentralPubMedCrossRef
25.
go back to reference Fleisch H. Bisphosphonates in bone disease: from the laboratory to the patient. 4th ed. Academic Press; San Diego 2000. Fleisch H. Bisphosphonates in bone disease: from the laboratory to the patient. 4th ed. Academic Press; San Diego 2000.
26.
go back to reference Ohtsubo-Yoshioka M, Nunomura S, Kataoka TR, Okayama Y, Ra C. Fc receptor beta chain deficiency exacerbates murine arthritis in the anti-type II collagen antibody-induced experimental model. Mod Rheumatol. 2013;23:804–10.PubMedCrossRef Ohtsubo-Yoshioka M, Nunomura S, Kataoka TR, Okayama Y, Ra C. Fc receptor beta chain deficiency exacerbates murine arthritis in the anti-type II collagen antibody-induced experimental model. Mod Rheumatol. 2013;23:804–10.PubMedCrossRef
Metadata
Title
Trabecular bone loss in collagen antibody-induced arthritis
Authors
Louise Grahnemo
Annica Andersson
Merja Nurkkala-Karlsson
Alexandra Stubelius
Marie K. Lagerquist
Mattias N. D. Svensson
Claes Ohlsson
Hans Carlsten
Ulrika Islander
Publication date
01-12-2015
Publisher
BioMed Central
Published in
Arthritis Research & Therapy / Issue 1/2015
Electronic ISSN: 1478-6362
DOI
https://doi.org/10.1186/s13075-015-0703-5

Other articles of this Issue 1/2015

Arthritis Research & Therapy 1/2015 Go to the issue
Live Webinar | 27-06-2024 | 18:00 (CEST)

Keynote webinar | Spotlight on medication adherence

Live: Thursday 27th June 2024, 18:00-19:30 (CEST)

WHO estimates that half of all patients worldwide are non-adherent to their prescribed medication. The consequences of poor adherence can be catastrophic, on both the individual and population level.

Join our expert panel to discover why you need to understand the drivers of non-adherence in your patients, and how you can optimize medication adherence in your clinics to drastically improve patient outcomes.

Prof. Kevin Dolgin
Prof. Florian Limbourg
Prof. Anoop Chauhan
Developed by: Springer Medicine
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.