The Hypoxia-Inducible Factor Pathway, Prolyl Hydroxylase Domain Protein Inhibitors, and Their Roles in Bone Repair and Regeneration

Table 1

Approaches to HIF signal enhancement.

Approach/agent	Remarks	Applications/reference
Chemical inhibition of PHDs by hypoxia-mimetics	Operate conveniently
Iron chelators or iron competitive inhibitors	Nonspecific; unwanted effects on endogenous iron
DFO		[38–44]
CoCl2		[45]
Oxoglutarate analogues	Nonspecific
DMOG		[40]
L-Mimosine		[43]
EDHB		[46]
FG-2216		[47]
GSK360A		[35]
Genetic techniques	Complex procedures; biotic security
Von-Hippel-Lindau knockout	Nonspecific	[48, 49]
PHD siRNA transfection	PHD-specific
PHD2 siRNA		[50, 51]
Constitutively active HIF-𝛼 transgenes	Organ-specific	[52, 53]

DFO: deferoxamine; CoCl₂: cobalt chloride; DMOG: dimethyloxalylglycine; EDHB: ethyl-3-4-dihydroxybenzoate; FG: fibrogen; GSK: GlaxoSmithKline.