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

Abstract

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.

Angiopoietin-2 gene polymorphisms are biomarkers for the development and progression of colorectal cancer in Han Chinese

“…A recent study has revealed that Angpt2 polymorphisms were associated with patients with resected colorectal liver metastases [29]. In this study, we extended our numbers of patients and controls from our previous study [30][31][32]. Our results reveal that smoking and alcohol consumption are significant risk factors for CRC (Table 1; p < 0.05 for both comparisons).…”

Soya-cerebroside inhibits VEGF-facilitated angiogenesis in endothelial progenitor cells

“…The c-Src/FAK, PI3 K/Akt and Raf/MEK signalling pathways regulate VEGF-mediated angiogenesis (Ribatti, 2016;Wu et al, 2018). In this study, we found that soya-cerebroside diminished VEGF-induced phosphorylation of c-Src and FAK, indicating that the c-Src/ FAK pathway is involved in the inhibitory effects of soya-cerebroside on angiogenesis.…”

“…Extracted proteins were resolved by SDS-PAGE and transferred to Immobilon® PVDF membranes. Western blot analysis was performed according to our previous reports Wu, Lin, Tsai, Huang, & Tang, 2018;Yang et al, 2019).…”

Prolotherapy for knee osteoarthritis using hypertonic dextrose vs other interventional treatments: systematic review of clinical trials

“…In animal models hypertonic dextrose increases fibroblast proliferation, collagen production and extracellular matrix in treated ligaments and tendons, [44,45] and it also generates a trophic effect in articular cartilage [46,47]. Additionally, a recent study reported that glucose decreased the expression of metalloproteinase 1 [48]. Similar effects have been reported in humans; for instance, Topol et al [34] studied individuals with severe knee OA through a histological evaluation and reported that hypertonic dextrose application had chondrogenic effects and induced the healing process at the expense of hyaline cartilage and fibrocartilage formation; while Reeves et al [35] reported a decrease in ligamentous laxity in patients with anterior cruciate ligament involvement when treated with hypertonic dextrose.…”