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. 2025 Aug 12;16:1611932. doi: 10.3389/fimmu.2025.1611932

Figure 2.

Diagram illustrating the signaling pathways of osteoblasts and osteoclasts influenced by reactive oxygen species (ROS). Osteoblasts involve RTK, PI3K, AKT, mTOR, WNT, GSK3β, β-catenin, PTCH1, SUFU, and GLI leading to bone formation and osteoblastogenesis. Osteoclasts involve RANKL, RANK, TRAF6, c-Src, Akt, IκB, NF-κB, MAPKs, ERK, JNK, p38, and NFATC1, promoting bone resorption and osteoclastogenesis.

Role of oxidative stress in bone remodeling high ROS levels inhibit Wnt/β-catenin and Hedgehog signaling, impairing osteoblast differentiation. Prolonged H2O2 exposure downregulates mTOR via AMPK-mediated Raptor phosphorylation, suppressing osteoblast proliferation. In osteoclasts, ROS accumulation due to mitochondrial activity promotes differentiation via RANKL-induced activation of TRAF6, NF-κB, and MAPK pathways, enhancing NFATc1 and c-Fos expression. ROS acts as a key regulator in bone homeostasis by modulating osteoblast and osteoclast activities through interconnected signaling pathways. ↑, decrease; ↓, increase. Created with BioRender.com.