J Bone Miner Res 2019 Apr 17. Epub 2019 Apr 17.
Veterans Affairs Nebraska-Western Iowa Health Care System, Research Service, Omaha, NE.
Objectives: Rheumatoid Arthritis (RA) is characterized by extra-articular involvement including lung disease, yet the mechanisms linking the two conditions are poorly understood. The collagen-induced arthritis (CIA) model was combined with the organic dust extract (ODE) airway inflammatory model to assess bone/joint-lung inflammatory outcomes.
Methods: DBA/1J mice were intranasally treated with saline or ODE daily for 5 weeks. CIA was induced on Days 1 and 21. Treatment groups included Sham (saline injection/saline inhalation); CIA (CIA/saline); ODE (saline/ODE); CIA+ODE (CIA/ODE). Arthritis inflammatory scores, bones, bronchoalveolar lavage fluid, lung tissues, and serum were assessed.
Results: In DBA/1J male mice, arthritis was increased in CIA+ODE>CIA>ODE vs. Sham. Micro-CT demonstrated loss of bone mineral density and volume and deterioration of bone micro-architecture to be greatest in CIA+ODE. However, ODE-induced airway neutrophil influx and inflammatory cytokine/chemokine levels in lavage fluids were increased in ODE>CIA+ODE vs. sham. Activated lung CD11c CD11b macrophages were increased in ODE>CIA+ODE>CIA pattern while lung hyaluronan, fibronectin, and amphiregulin levels were greatest in CIA+ODE. Serum autoantibody and inflammatory marker concentrations varied among experimental groups. Compared to male mice, female mice showed less articular and pulmonary disease.
Conclusion: The interaction of inhalation induced airway inflammation and arthritis induction resulted in compartmentalized responses with the greatest degree of arthritis and bone loss in male mice with combined exposures. Data also support suppression of the lung inflammatory response but increases in extracellular matrix protein deposition/interstitial disease in the setting of arthritis. This co-exposure model could be exploited to better understand and treat RA-lung disease. This article is protected by copyright. All rights reserved.