15-Lipoxygenase-1 in osteoblasts promotes TGF-β1 expression via inhibiting autophagy in human osteoarthritis - 30/11/19
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Graphical abstract |
Highlights |
• | The expression levels of 15-LOX-1 and TGF-β1 were higher in OA subchondral bone than that in non-OA subchondral bone. |
• | 15-LOX-1, which downregulated autophagy by inhibiting AMPK following activation of mTORC1, increased the expression of TGF-β1. |
• | Treatment with autophagy inhibitors significantly increased the expression levels of TGF-β1 in osteoblasts. |
Abstract |
Background |
15-Lipoxygenase-1 (15-LOX-1) belongs to the lipoxygenase family involved in the inflammatory response and pathological process of various diseases, including osteoarthritis (OA). The overexpression of TGF-β1 in osteoblasts leads to abnormal changes in subchondral bone structure, eventually causing OA. However, the pathogenesis of the disease is poorly defined, and the interaction between 15-LOX-1 and TGF-β1 in osteoblasts has not been evaluated in OA. In this study, the role of 15-LOX-1 in subchondral bone osteoblasts in OA was evaluated.
Method |
15-LOX-1 expression in osteoblasts of the subchondral bone of patients with OA was measured by immunohistochemistry, qRT-PCR, and western blotting. Osteoblasts extracted from the subchondral bone of OA were transfected with 15-LOX-1 siRNA and an overexpression vector. The eff ;ect of 15-LOX-1 on the expression of TGF-β1 in OA osteoblasts was assessed by qRT-PCR and western blotting. The effect of 15-LOX-1 on autophagy via AMPK pathway in OA osteoblasts was evaluated by qRT-PCR, western blotting, and transmission electron microscopy.
Results |
The expression levels of 15-LOX-1 and TGF-β1 were higher in OA subchondral bone osteoblast than that in non-OA subchondral bone. 15-LOX-1, which downregulated autophagy by inhibiting AMPK following the activation of mTORC1, upregulated the osteoblast expression of TGF-β1. Treatment with autophagy inhibitors significantly increased the expression levels of TGF-β1 in osteoblasts.
Conclusion |
In the present study, our findings suggested that 15-Lipoxygenase-1 in Osteoblasts Promotes TGF-β1 expression via inhibiting autophagy in human Osteoarthritis. These novel results suggested that 15-Lipoxygenase-1 expressed by subchondral bone osteoblasts might be a promising therapeutic target in human OA.
Le texte complet de cet article est disponible en PDF.Abbreviations : 15-LOX-1, 3MA, CQ, mTOR, OA, qRT-PCR, TGF-β1, AMPK
Keywords : Osteoarthritis, Subchondral bone, 15-LOX-1, TGF-β1, AMPK, mTORC1, Autophagy
Plan
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