TWEAK promotes osteoclastogenesis in rheumatoid arthritis

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Title
TWEAK promotes osteoclastogenesis in rheumatoid arthritis
Author(s)
J S Park; S K Kwok; M A Lim; H J Oh; E K Kim; J Y Jhun; J H Ju; K S Park; Young Woo Park; S H Park; H Y Kim; Y G Cho; M L Cho
Bibliographic Citation
American Journal of Pathology, vol. 183, no. 3, pp. 857-867
Publication Year
2013
Abstract
Bone destruction is critical in the functional disability of patients with rheumatoid arthritis (RA). Osteoclasts, specialized bone-resorbing cells regulated by cytokines, such as receptor activator of NF-κB ligand (RANKL), are primarily implicated in bone destruction in RA. The aim of the study was to examine whether tumor necrosis factor-like weak inducer of apoptosis (TWEAK), a member of the tumor necrosis factor superfamily, has osteoclastogenic activity in patients with RA and in animal models, including mice with collagen-induced arthritis (CIA) and IL-1 receptor antagonist knockout (IL-1RaKO) mice. TWEAK was increased in the synovium, synovial fluid, and serum of patients with RA and in the synovium of CIA mice and IL-1RaKO mice. TWEAK induced RANKL expression in mixed joint cells and splenocytes from CIA mice, IL-1RaKO mice, and fibroblast-like synoviocytes from patients with RA. Both osteoclast precursor cells and osteoclasts express TWEAK receptor fibroblast growth factor-inducible 14. In addition, TWEAK enhanced in vitro osteoclastogenesis without the presence of RANKL-providing cells and by inducing RANKL expression in fibroblast-like synoviocytes. Moreover, treatment with fibroblast growth factor-inducible 14-Fc inhibited RANKL-induced osteoclastogenesis, indicating that endogenous TWEAK also has osteoclastogenic activity. Our data demonstrated that TWEAK promotes osteoclastogenesis in RA, suggesting that therapeutic strategies targeting TWEAK could be effective for treatment of patients with RA, especially in preventing bone destruction.
ISSN
0002-9440
Publisher
Elsevier
DOI
http://dx.doi.org/10.1016/j.ajpath.2013.05.027
Type
Article
Appears in Collections:
1. Journal Articles > Journal Articles
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