Bortezomib prevents the expression of MMP-13 and the degradation of collagen type 2 in human chondrocytes.

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.

authors

Hu W,Zhang W,Li F,Guo F,Chen A

doi

10.1016/j.bbrc.2014.08.102

subject

Has Abstract

pub_date

2014-09-26 00:00:00

pages

526-30

issue

3

eissn

0006-291X

issn

1090-2104

pii

S0006-291X(14)01534-4

journal_volume

452

pub_type

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