Premium
Glucose suppresses IL‐1β‐induced MMP‐1 expression through the FAK, MEK, ERK, and AP‐1 signaling pathways
Author(s) -
Wu TsungJu,
Lin ChihYang,
Tsai ChunHao,
Huang YuanLi,
Tang ChihHsin
Publication year - 2018
Publication title -
environmental toxicology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.813
H-Index - 77
eISSN - 1522-7278
pISSN - 1520-4081
DOI - 10.1002/tox.22618
Subject(s) - mapk/erk pathway , matrix metalloproteinase , proinflammatory cytokine , chemistry , signal transduction , microbiology and biotechnology , cancer research , focal adhesion , small interfering rna , mek inhibitor , kinase , phosphorylation , pharmacology , endocrinology , medicine , inflammation , biology , biochemistry , transfection , gene
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.