Moreover, Nox4 is implicated in the RANKL-mediated abnormal enhancement of osteoclast differentiation in T2DM through mitochondrial ROS [119], which serve as secondary messengers in various signaling pathways such as MAPK, NF-κB, and Ca2+, ultimately upregulating NFATc1 expression to facilitate osteoclast differentiation and function [120,121]. This evidence concerns the gene NOX4 and type 2 diabetes mellitus.