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

Table 1.

Mechanistic studies of inflammation and oxidative stress in osteoporotic bone remodeling.

Study Model type Target pathways or molecules Main findings Reference
Effect of H2O2 on osteoblasts In vitro (HEK293 cells) mTORC1, AMPK Low-dose H2O2 promotes proliferation via mTORC1; high-dose inhibits proliferation and suppresses Wnt/β-catenin signaling (10)
High-fat culture environment In vitro (primary murine osteoblasts) ROS, Wnt/β-catenin Elevated ROS inhibits Wnt/β-catenin signaling and osteoblast differentiation; promotes adipogenic gene expression (11)
OVX mouse model In vivo (ovariectomized mice)  IL-1β, TNF-α, NLRP3 inflammasome Pro-inflammatory cytokines are upregulated; NLRP3 knockout reduces inflammatory marker expression (12)
RANKL-induced osteoclastogenesis In vitro (mouse/human osteoclast precursors) TRAF6, NF-κB, MAPK, NFATc1 ROS enhance osteoclastogenesis through activation of NF-κB and MAPKs (13, 14)
Ethanol-induced ROS production In vitro (human osteoblasts) RANKL/OPG Ethanol upregulates RANKL via ROS; inhibited by NAC or 17β-estradiol (15)
IL-6-mediated osteoclastogenesis In vitro (mouse osteoclast precursors) JAK/STAT, S1PR2 IL-6 enhances osteoclast migration and activity; upregulates S1PR2 (16)
IL-11 and bone loss Knockout/transgenic mice JAK1/STAT3, RANKL/OPG IL-11 promotes bone resorption; IL-11R knockout improves bone volume and osteoblast activity (17, 18)
IL-17-driven bone loss In vivo (OVX mice) CXCR3/CCL20, RANKL IL-17 increases RANK sensitivity; blockade reverses OVX-induced bone loss (19, 20)
Antioxidant NAC intervention In vitro + in vivo ROS, GSH/Nrf2 NAC alleviates bone erosion and oxidative stress (21)
Drynaria fortunei extract In vitro + in vivo SIRT1/Notch1, NLRP3 inflammasome Downregulates IL-1β, TNF-α; suppresses osteoclastogenesis (22)
Resveratrol and osteogenesis In vitro (human BMSCs)/animal Wnt/β-catenin, Runx2, GSK3β Enhances osteogenesis via β-catenin stabilization; prevents bone loss (23)
Ebselen antioxidant therapy In vivo (OA rats), in vitro (BMSCs, osteoclasts) PI3K/Akt, RANKL/OPG Inhibits osteoclastogenesis and oxidative injury; promotes osteoblast function (24, 25)

Representative experimental studies elucidating the molecular mechanisms by which inflammation and oxidative stress contribute to osteoporosis. The table summarizes model systems, key molecular targets, primary findings, and corresponding references.