T-2 toxin induces articular cartilage damage by increasing the expression of MMP-13 via the TGF-β receptor pathway

Abstract

T-2 toxin pre-disposes individuals to osteoarthritis, Kashin–Beck disease (KBD). The major pathological change associated with KBD is the degradation of the articular cartilage matrix. Herein, we investigated the key molecules that regulate T-2 toxin-mediated cartilage degradation. Potential KBD treatments were also investigated. Sprague Dawley rats were divided into the T-2 toxin group and the control group. The T-2 toxin group received 100 ng/g BW/day, whereas the control group received a similar dose of PBS. The expression of matrix metalloproteinase-13 (MMP-13) and TGF-β receptor I/II (TGF-βRI/II) was analyzed using immunohistochemical staining. C28/I2 chondrocytes were exposed to TGF-βRI/II binding inhibitor (GW788388) for 24 h before incubation in different T-2 toxin concentrations (0, 6, 12, and 24 ng/mL for 72 h). The expression of mRNA for TGF-βRI/II, MMP-13 and proteins for MMP-13, and Smad-2 in chondrocytes were analyzed using RT-PCR and western blot, respectively. Safranin O staining revealed that T-2 toxin treatment modulated the expression of articular cartilage matrix. On the other hand, T-2 toxin treatment sharply increased the expression of MMP-13, TGF-βRI, and TGF-βRII in the rat cartilages. Interestingly, blocking the TGF-βRs-smad 2 signaling pathway using GW788388 abrogated the effect of T-2 toxin on upregulating MMP-13 expression. The expression of MMP-13 in chondrocytes induced with T-2 toxin is regulated via the TGF-βRs signaling pathway. As such, inhibiting the expression of TGF-βRs is a potential KBD treatment.