Table 3.

Examples of hypoxia sensitive genes in signaling and hormonal pathways identified recently by Baron et al.23 to play essential roles in bone growth

Mechanism	Hypoxia‐sensitive gene	Effect
CNP signaling	NPR2	VEGFA receptor NPR2 plays a role in chondrocyte development and seems to be related to hypoxia‐inducible growth factor‐α43
FGF signaling	FGFR3	Hypoxia induces FGFR3 signaling.44 FGFR3 plays a role in human achondroplasia45
Cartilage matrix	ACAN	Hypoxia upregulates ACAN, a member of the aggrecan/versican proteoglycan family. The encoded protein is an integral part of the extracellular matrix in cartilagenous tissue46
Transcription	SOX9	Hypoxia increases nuclear‐expressed MIF (macrophage migration inhibitory factor) which acts as a transcriptional regulator by interacting with the promoter of SOX9.47 MIF plays a role in fracture healing48
Epigenetic control	DNMT3A	Hypoxia mimetic deferoxamine influences expression of histone acetylation‐ and DNA methylation‐associated genes in osteoblasts49
Thyroid hormone signaling	PAX8	This gene plays a role in the mechanisms through which thyroid hormones modulate bone growth50