TABLE 2.

Potential clinical interventions targeting iron overload for the treatment of OA.

Therapeutic targets	Agents	Effects	References
Chondrocytes	Deferoxamine	Inhibit oxidative stress and mitochondrial dysfunction	Jing et al. (2021a)
		Reduce IL-1β-induced matrix-degrading enzymes production	Jing et al. (2020)
	BAPTA-AM	Blunt iron influx through regulating TfR1 internalization	Jing et al. (2021b)
	D-mannose	Protect chondrocytes from ferroptosis by eliminating HIF-2α-dependent lipid peroxide accumulation	Zhou et al. (2021b)
Osteoclasts	Lactoferrin	Suppress osteoclast differentiation via reducing the RANKL/OPG ratio	Hou et al. (2012a)
	Deferoxamine	Inhibit osteoclast formation by negative regulation of MAPK signaling	Zhang et al. (2019)
Osteoblasts	Melatonin	Prevent osteogenic differentiation by inhibiting ROS production and p53/ERK/p38 activation	Yang et al. (2017)
	Icariin	Promote osteoblast survival by preventing mitochondrial membrane potential dysfunction and ROS production	Jing et al. (2019)
Iron metabolic kinetics	Hepcidin	Rescue impaired bone formation caused by FAC treatment via regulating iron absorption	Jiang et al. (2019)