Therefore, we first compared the AREG levels of normal human synovial fibroblast (normal SF) and OASF. The Western blot and qPCR results displayed in Figures 1(a) and 1(b) indicate that the protein levels and mRNA expression of AREG were higher in the OASFs than in the normal SFs.
AREG/EGFR Interaction Caused the Expression of MMP-13 in OASF. All EGF-like ligands affect cell functions by binding to EGFR [24].
Therefore, we explored the signaling pathways involved in AREG-induced MMP-13 production in human OA synovial fibroblasts (OASFs), as well as the role that AREG plays in the pathogenesis of OA, to determine whether AREG is an appropriate target for drug intervention in OA in the future.
AREG caused a significant increase in the phosphorylation of p85 and Akt in OASFs (Figure 3(d)).
The stimulation of OASFs by using AREG increased IKK[alpha]/[beta], I[kappa]B[alpha], and p65 phosphorylation in a time-dependent manner (Figure 4(c)).
The results of our study indicated that AREG protein levels were significantly higher in OASFs than in normal SFs.
We discovered that AREG induces MMP-13 mRNA and protein expression in a dose- and time-dependent manner in OASFs. We also demonstrated that AREG-induced MMP-13 production requires activation of the EGFR, PI3K, Akt, and NF-[kappa]B signaling pathways.
In human knee OA synovial fibroblasts (
OASFs), adiponectin was found to induce expression of ICAM-1 via the liver kinase (LK) B1/calmodulin-dependent protein kinase II (CaMKII), AMPK, c-Jun, and AP-1 signaling pathway and this expression increased the adhesion of monocytes to human
OASFs (Figure 4 and Table 1) [151].