title: Kinetics and interplay of mediators of inflammation-induced bone damage in the course of adjuvant arthritis.
abstract: Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation, bone erosion, and cartilage destruction in the joints. It is increasingly being realized that inflammation might play an important role in inducing bone damage in arthritis. However, there is limited validation of this concept in vivo in well-controlled experimental conditions. We addressed this issue using the adjuvant arthritis (AA) model of RA. In AA, the draining lymph nodes are the main sites of activation of pathogenic leukocytes, which then migrate into the joints leading to the induction of arthritis. We tested the temporal kinetics of mediators of bone damage [e.g., receptor activator of nuclear factor kappa-B ligand (RANKL), osteoprotegerin (OPG) and osteopontin (OPN)] and inflammation (pro-inflammatory cytokines and chemokines) in the draining lymph node cells (LNC) at different phases of AA, and then examined their inter-relationships. Our study revealed that, together with cytokines/chemokines, some of the mediators of bone remodeling are also produced in LNC. Various cytokines/chemokines showed distinct kinetics of expression as well as patterns of correlation with mediators of bone remodeling at different phases of the disease. Pro-inflammatory cytokines such as TNF-alpha are known to play an important role in bone damage. Interestingly, there was a positive correlation between TNF-alpha and RANKL, between RANKL and each of the 3 chemokines tested (RANTES, MIP-1alpha, and GRO/KC), and between TNF-alpha and RANTES. Our results in the AA model lend support to the concept of osteo-immune crosstalk during the course of autoimmune arthritis.
authors.affiliation: Department of Microbiology and Immunology, University of Maryland School of Medicine, Baltimore, MD, USA.
authors.forename: S M
authors.initials: SM
authors.lastname: Nanjundaiah
authors.forename: J P
authors.initials: JP
authors.lastname: Stains
authors.forename: K D
authors.initials: KD
authors.lastname: Moudgil
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000276:immunology* / Q000473:pathology; D016723:Bone Remodeling / Q000276:immunology; D002478:Cells, Cultured; D016207:Cytokines / Q000276:immunology*; D007249:Inflammation / Q000276:immunology; D007700:Kinetics; D008198:Lymph Nodes / Q000166:cytology / Q000276:immunology; D008297:Male; D053244:Osteoprotegerin / Q000276:immunology; D051381:Rats; D011917:Rats, Inbred Lew
chemical_list: D016207:Cytokines; D053244:Osteoprotegerin