Iron dysregulation, ferroptosis, and oxidative stress in diabetic osteoporosis: Mechanisms, bone metabolism disruption, and therapeutic strategies

Table 2 The role of inflammatory response, oxidative stress, and high-throughput sequencing in diabetic osteoporosis

Mechanism type	Key factor	Pathway	Impact on bone metabolism	Ref.
Inflammatory response	TNF-α	Activates NF-κB pathway, promotes osteoclast differentiation and activity	Increases bone resorption, leading to osteoporosis	Qi et al[20]
	IL-6	Stimulates RANKL expression, enhances osteoclast formation	Increases bone resorption, decreases bone density	Wu et al[4]
Oxidative stress	ROS	Damages osteoblasts, inhibits differentiation and function	Reduces bone formation, promotes osteoporosis	Iantomasi et al[53]
	AGEs	Binds to receptors, induces oxidative stress and inflammatory responses	Disrupts bone matrix, reduces bone strength	Wang et al[26], Zhang et al[27]
High-throughput sequencing	miRNAs	Identifies differentially expressed miRNAs (e.g., miR-140-5p, miR-486-3p) involved in bone metabolism pathways like Wnt and TGF-β signaling	Predicts osteoporosis progression; regulates osteoblast and osteoclast activities through gene silencing or activation	Huang et al[110]
RNA-seq	Transcript variants (e.g., ATF3)	Detects oxidative stress-induced transcriptomic changes, including activation of TNF and NRF2 signaling pathways	Highlights mitochondrial dysfunction and inflammation contributing to bone loss	Nyunt et al[111], Chen et al[112]

AGEs: Advanced glycation end products, bind to their receptors to induce oxidative stress and inflammatory responses, disrupting the bone matrix and reducing bone strength; IL-6: Interleukin-6, a pro-inflammatory cytokine that stimulates the expression of receptor activator of nuclear factor-κB ligand, enhancing osteoclast formation; NF-κB: Nuclear factor-κB, a key transcription factor involved in regulating inflammatory responses and immune processes; activation of nuclear factor-κB promotes osteoclast differentiation and activity; RANKL: Receptor activator of nuclear factor-κB ligand; ROS: Reactive oxygen species, high levels of reactive oxygen species damage osteoblasts, inhibit their differentiation and function, and reduce bone formation; TNF-α: Tumor necrosis factor-α, a pro-inflammatory cytokine that activates the nuclear factor-κB pathway, promoting osteoclast differentiation and activity.