Matrix metalloproteinase-13 expression in IL-1β-treated chondrocytes by activation of the p38 MAPK/c-Fos/AP-1 and JAK/STAT pathways

Abstract

Matrix metalloproteinase-13 (MMP-13, mammalian collagenase) degrades the cartilage matrix in pathological conditions such as osteoarthritis. Here, to establish the signaling pathway to MMP-13 induction, effects of mitogen-activated protein kinase (MAPK) pathway and the possibility of some other signaling pathways involved are investigated in interleukin-1β (IL-1β)-treated human chondrosarcoma cell line, SW1353 cells. IL-1β (10 ng/mL) treatment induced MMP-13 in SW1353 cells, with concomitant activation of nuclear factor-κB, activator protein-1 (AP-1) and MAPKs, including extracellular signal-regulated protein kinase, p38 MAPK and c-Jun N-terminal kinase. Among these MAPKs, only p38 MAPK inhibitor (SB203580) blocked MMP-13 induction and AP-1 activation in IL-1β-treated SW1353 cells. SB203580 also inhibited c-Fos translocation to the nucleus (but not c-Jun). Importantly, IL-1β treatment induced Janus kinase 2 (JAK2) and signal transducer and activator of transcription 1/2 (STAT1/2) activation. The JAK2 inhibitor (AG490) blocked STAT1/2 activation as well as MMP-13 induction in IL-1β-treated SW1353 cells. STAT1/2 siRNA transfection also reduced MMP-13 expression levels. Thus, from the present study, it is concluded that p38 MAPK/c-Fos/AP-1 and JAK2/STAT1/2 are involved in MMP-13 induction of IL-1β-treated human chondrocytes, SW1353 cells. Blocking these signaling pathways may have chondroprotective effects in cartilage degeneration.

Effects of Flavonoids on Matrix Metalloproteinase-13 Expression of Interleukin-1β–Treated Articular Chondrocytes and Their Cellular Mechanisms: Inhibition of c-Fos/AP-1 and JAK/STAT Signaling Pathways

“…In particular, STAT1/2 activation is involved in IL-1β-treated SW1353 cells (21). When the cells were treated with apigenin, STAT1/2 activation was considerably inhibited in a concentration-dependent manner (Fig.…”

“…From the same media, MMP-13 expression was also examined by Western blotting analysis. The optimum expression time of MMP-13 and other signaling molecules was determined in the previous study (21). In brief, media was concentrated with TCA and acetone.…”

“…4b). However, the inhibitory action of JNK activation is not likely a major inhibitory mechanism of apigenin against MMP-13 expression because the potency of inhibition is very weak and the JNK pathway is not primarily involved in AP-1 activation and MMP-13 expression in IL-1β-treated SW1353 cells (21).…”

Resveratrol attenuates matrix metalloproteinase-9 and -2- regulated differentiation of HTB94 chondrosarcoma cells through the p38 kinase and JNK pathways

“…The p38 MAPK/c-Fos/AP-1 and JAK2/STAT1/2 pathways are involved in MMP-13 induction in IL-1β-treated HTB94 human chondrocytes. Blocking these signaling pathways may have chondroprotective effects in cartilage degeneration (27). Another study demonstrated downregulation of MMP-13 by the root extract of Cyathula officinalis Kuan and its constituents in IL-1β-treated chondrocytes.…”

Histone Deacetylase Inhibitor Vorinostat (SAHA) Suppresses IL-1β–Induced Matrix Metallopeptidase-13 Expression by Inhibiting IL-6 in Osteoarthritis Chondrocyte

“…33 MMP-13 expression in chondrocytes also is modulated by the c-Jun N-terminal kinase and NFkB signaling pathways. 34 Previous studies have shown that SAHA selectively attenuates mitogen-activated protein kinase and NF-kB signaling activity in IL-1beinduced human OA chondrocytes.…”