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A new class of osteoarthritis therapeutic, extracellular matrix protection factor, alters cytokine production in chondrocytes (922.12)
Author(s) -
Docherty Courtney,
Belogorodsky Dimitry,
Cho Ellen,
Chmielewski Sarah,
Lopez Samuel,
Holmes Tiffany,
D'Angelo Marina
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.922.12
Subject(s) - cytokine , cartilage , extracellular matrix , matrix metalloproteinase , transforming growth factor , osteoarthritis , microbiology and biotechnology , tumor necrosis factor alpha , immunology , proteases , chondrocyte , chemistry , medicine , biology , pathology , anatomy , biochemistry , enzyme , alternative medicine
Articular cartilage damage leads to osteoarthritis (OA), a disease characterized by altered cartilage homeostasis. Several cellular elements including growth factors and proteases are involved in this pathology. Our lab has developed a new class of therapeutic, extracellular matrix protection factors (ECPFs), that protect cartilage from the devastation associated with OA. ECPF‐1 targets the interaction between matrix metalloprotease 13 (MMP‐13) and transforming growth factor β (TGF‐β), but the cellular mechanism of ECPF‐1 chondroprotection is unknown. Inflammatory cytokines play a role in the pathology associated with OA, and are regulated, in some part, by TGF‐β biology. To test the downstream effects of blocking TGF‐β activation on cytokine production, cultured chondrocytes from embryonic avian sterna were treated for 24 hours with ECPF‐1 at 250nM, 2.5μM and 5.0μM concentrations and the production of the inflammatory cytokines, IL‐1β and TNF‐α, were monitored. Activated TGF‐β was reduced and production of IL‐1β and TNF‐α were decreased in response to ECPF‐1 treatment including an unexpected increase in these cytokines following 5.0μM addition of ECPF‐1. This biphasic effect of ECPF‐1 indicates a duality to the protective therapeutic nature and overall mechanism of action of ECPF‐1 in the protection of articular cartilage.