Fig. 10: A schematic model of the molecular mechanism underlying the role of AGE-RAGE signaling in the meniscus. | Experimental & Molecular Medicine

Fig. 10: A schematic model of the molecular mechanism underlying the role of AGE-RAGE signaling in the meniscus.

From: Advanced glycation end products promote meniscal calcification by activating the mTOR-ATF4 positive feedback loop

Fig. 10

In the left panel, a normal meniscus without abnormal neovascularization was observed, exhibiting well-aligned fibers and optimal biomechanical properties. Most of the ATF4 protein in meniscal cells is degraded via the ubiquitination pathway, and there is no significant mTOR activation. The right panel shows that meniscal vessels introduce a significant amount of AGEs with increasing age or glucose levels, which promotes neoangiogenesis and osteogenic differentiation of meniscal cells. AGEs and RAGE activate the ATF4-mTOR positive feedback loop, where mTOR inhibits the degradation of ATF4 by decreasing its ubiquitination. Simultaneously, ATF4 activated mTOR by elevating arginine uptake, eventually leading to calcification of the meniscus and impairment of its biomechanical properties. The schematic was constructed using Figdraw.

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