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Environ Toxicol. 2018 Oct;33(10):1061-1068. doi: 10.1002/tox.22618. Epub 2018 Aug 11.

Glucose suppresses IL-1β-induced MMP-1 expression through the FAK, MEK, ERK, and AP-1 signaling pathways.

Wu TJ1,2, Lin CY1,3, Tsai CH4,5, Huang YL6, Tang CH1,4,6,7.

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Graduate Institute of Basic Medical Science, China Medical University, Taichung, Taiwan.
Department of Physical Medicine and Rehabilitation, Changhua Christian Hospital, Changhua, Taiwan.
Department of Medicine, Mackay Medical College, New Taipei City, Taiwan.
School of Medicine, China Medical University, Taichung, Taiwan.
Department of Orthopedic Surgery, China Medical University Hospital, Taichung, Taiwan.
Department of Biotechnology, College of Health Science, Asia University, Taichung, Taiwan.
Chinese Medicine Research Center, China Medical University, Taichung, Taiwan.


Osteoarthritis (OA) commonly affects the synovial joint and is characterized by degradation of articular cartilage. Increased matrix metalloproteinase (MMP) activity plays a major role in this degradation. Dextrose (D-glucose) prolotherapy has shown promising activity in the treatment of different musculoskeletal disorders, including OA. However, little is known about the role of glucose on MMP inhibition in OA therapy. We found that stimulating chondrocytes with the proinflammatory cytokine interleukin-1β (IL-1β) increased the expression of MMP-1, MMP-3, and MMP-13. Glucose reduced this increase in MMP-1 expression, but had no effect upon MMP-3 or MMP-13 expression. Analyses using a focal adhesion kinase (FAK) inhibitor, MEK inhibitors (U0126 and PD98059), an ERK inhibitor, AP-1 inhibitors (curcumin and tanshinone), or siRNAs demonstrated that the FAK, MEK, ERK, and AP-1 pathways mediate IL-1β-induced increases in MMP-1 expression. Glucose antagonized IL-1β-promoted phosphorylation of FAK, MEK, ERK, and c-Jun. Thus, glucose decreased IL-1β-induced MMP-1 expression through the FAK, MEK, ERK, and AP-1 signaling cascades. These findings may provide a better understanding of the mechanisms of prolotherapy on inhibiting MMP expression.


IL-1β; MMP-1; chondrocytes; glucose; osteoarthritis

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