Abstract:
:The structural backbone of extracellular matrix in cartilage is the collagen fibril, which is mainly composed of type II collagen. A measurable increase in type II collagen denaturation and degradation has been found in early Osteoarthritis (OA). Pro-inflammatory cytokine such as TNF-α produced in OA cartilage induced the expression of matrix metalloproteinase-13 (MMP-13), which targets and degrades type II collagen. Bortezomib is a proteasome inhibitor approved by the FDA for treatment of multiple myeloma and mantel cell lymphoma. The effects of bortezomib in OA have not been reported before. In this study, we found that bortezomib is able to suppress the degradation of type II collagen induced by TNF-α in human chondrocytes. Mechanistically, bortezomib treatment inhibits the expression of IRF-1 through blunting JAK2/STAT1 pathway, thereby prevents the induction of MMP-13 as well as the degradation of type II collagen. Our findings suggest the therapeutic potentials of bortezomib in patients with OA.
journal_name
Biochem Biophys Res Communjournal_title
Biochemical and biophysical research communicationsauthors
Hu W,Zhang W,Li F,Guo F,Chen Adoi
10.1016/j.bbrc.2014.08.102subject
Has Abstractpub_date
2014-09-26 00:00:00pages
526-30issue
3eissn
0006-291Xissn
1090-2104pii
S0006-291X(14)01534-4journal_volume
452pub_type
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