Inhibition of the TGF-β1/Smad signaling pathway protects against cartilage injury and osteoarthritis in a rat model

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Abstract

Transforming growth factor-β1 (TGF-β1) in osteoblastic cells triggers pathological changes observed in osteoarthritis (OA). Thus, we hypothesized that the inhibition of the TGF-β1/Smad signaling pathway could act to protect against cartilage injury in rats with OA. After establishment of rat models induced by papain and L-cysteine, rats were subsequently assigned into the TβRI inhibitors, normal control (NC) and OA model groups. RT-qPCR and western blotting were performed to determine mRNA and protein expressions of TGFβ1, Smad2, Smad3 and Activin receptor-like kinase 5 (ALK5), respectively. Immunofluorescence staining was used to detect the expression of collagen X (COLX). Immunohistochemical staining was used to determine the expression of the specific transcription factor Osterix as well as TGF-β1 related factors. Increased expression levels of TGFβ1, Smad2, Smad3 and ALK5in the OA model group were higher than those in the TβRI inhibitors group. Compared with the NC group, the OA model groups exhibited elevated expressions of TGF-β1, p-Smad2/3 and ALK5 in the TGF-β1 signaling pathway, and elevated numbers of COLX and Osterix positive cells. The rats in the TβRI inhibitors group had decreased expressions of p-Smad2/3 and ALK5, as well as decreased COLX and Osterix positive cells when compared with OA model group. However, these levels were still higher than that of the NC group. Our findings suggested that up-regulation of TGF-β1 inhibited the TGF-β1/Smad signaling pathway acting to alleviate OA, thus highlighting the potential of the TGF-β1/Smad signaling pathway as a therapeutic target for treatment of OA.

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