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

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 nnetalloproteinase-13 (MMP-13) and TGF-beta receptor I/II (TGF-beta RI/II) was analyzed using immunohistochemical staining. C28/12 chondrocytes were exposed to TGF-beta RI/I 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 nnRNA for TGF-beta RI/II, MMP-13 and proteins for MMP-13, and Smad-2 in chondrocytes were analyzed using RTPCR 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-beta RI, and TGF-beta RII in the rat cartilages. Interestingly, blocking the TGF-beta Rs-smad 2 signaling pathway using GW788388 abrogated the effect of T-2 toxin on upregulating M MP-13 expression. The expression of MMP-13 in chondrocytes induced with T-2 toxin is regulated via the TGF-beta Rs signaling pathway. As such, inhibiting the expression of TGF-beta Rs is a potential KBD treatment.

Automated summary

The study investigates the key molecules that regulate T-2 toxin-mediated cartilage degradation and potential treatments for Kashin-Beck disease (KBD). The expression of MMP-13 and TGF-beta RI/II was analyzed in rats treated with T-2 toxin. In chondrocytes, the expression of mRNA for TGF-beta RI/II, MMP-13, and proteins for MMP-13 and Smad-2 were analyzed. The findings suggest that inhibiting the expression of TGF-beta Rs is a potential treatment for KBD.