Plasminogen activator inhibitor-1 is involved in interleukin-1β-induced matrix metalloproteinase expression in murine chondrocytes

Abstract

Objectives: Interleukin (IL)-1β and matrix metalloproteinases (MMPs) play important roles in the pathogenesis of osteoarthritis. On the other hand, plasminogen activator inhibitor-1 (PAI-1), an inhibitor of fibrinolysis, exerts functions in the pathogenesis of various diseases. However, the functional roles of PAI-1 in the chondrocytes have been still remained unknown.

Methods: In the present study, we investigated the roles of PAI-1 in the effects of IL-1β on the chondrocytes using wild-type and PAI-1-deficient mice.

Results: IL-1β significantly elevated PAI-1 mRNA levels in the chondrocytes from wild-type mice. PAI-1 deficiency significantly blunted the mRNA levels of TGF-β and IL-6 enhanced by IL-1β in murine chondrocytes. Moreover, PAI-1 deficiency significantly decreased the mRNA levels of MMP-13, -3 and -9 as well as MMP-13 activity enhanced by IL-1β in the chondrocytes. In addition, PAI-1 deficiency significantly reversed type II collagen mRNA levels suppressed by IL-1β in the chondrocytes. On the other hand, active PAI-1 treatment significantly enhanced the mRNA levels of MMP-13, -3 and -9 as well as decreased type II collagen mRNA levels in the chondrocytes from wild-type mice.

Conclusion: We first demonstrated that PAI-1 is involved in MMP expression enhanced by IL-1β in murine chondrocytes. PAI-1 might be crucial for the cartilage matrix degradation and the impaired chondrogenesis by IL-1β in mice.

Keywords:

• Chondrocyte
• interleukin-1β
• matrix metalloproteinase
• osteoarthritis
• plasminogen activator inhibitor-1

Conflict of interest

None.

Additional information

Funding

This study was partly supported by a grant from the Takeda Science Foundation to N. K. and a Grant-in-Aid for Scientific Research C: 16K08534 to N. K., 15K08220 to H. K. and a Grant-in-Aid for Scientific Research on Innovative Areas (grant number 15H05935, “Living in Space”) from the Ministry of Education, Culture, Sports, Science, and Technology of Japan.