Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement
Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.
In Vivo Gene Transfer of IL-17A Induces Osteoclast Formation in a RANKL-Dependent Manner, Exacerbates Collagen-Induced Arthritis and Induces Epidermal Hyperplasia.
Adamopoulos1, Iannis E., Chao2, Cheng-Chi, Bowman3, Eddie P.
Rheumatoid arthritis is an autoimmune disease where the interaction between the activated immune system and the skeletal system results in bone loss. We have previously shown that IL-17A upregulates the receptor RANK on human osteoclast precursors to increase their responsiveness to RANKL leading to increased bone loss in vitro.
In this study, we used minicircle-mediated gene transfer to evaluate the in vivo interplay between IL-17A and RANKL on bone metabolism.
Chronic systemic IL-17A exposure induces neutrophilia in vivo, but was not sufficient to drive synovial inflammation in a naïve C57Bl/6 mouse. Systemic IL-17A exposure in vivo sensitized osteoclast precursors to sub-optimal RANKL levels resulting in elevated serum TRAP levels. The serum TRAP induction was independent of arthritis development. Moreover, systemic IL-17A exposure prior to collagen-induced arthritis sensitization severely exacerbated arthritis and bone loss, and led to epidermal hyperplasia.
Collectively our data suggest that IL-17A may play distinct roles in bone loss, joint inflammation and psoriasis making it a suitable candidate to combat psoriatic arthritis.
To cite this abstract, please use the following information:
Adamopoulos, Iannis E., Chao, Cheng-Chi, Bowman, Eddie P.; In Vivo Gene Transfer of IL-17A Induces Osteoclast Formation in a RANKL-Dependent Manner, Exacerbates Collagen-Induced Arthritis and Induces Epidermal Hyperplasia. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :1842