| Article ID | Journal | Published Year | Pages | File Type |
|---|---|---|---|---|
| 2093216 | Stem Cell Reports | 2016 | 14 Pages |
•The hypoxic microenvironment is disrupted in degenerative CEP•Hypoxia promotes chondrogenesis but inhibits osteogenesis in CESCs•Hypoxia regulates chondro-osteogenesis through HIF1A/MIF pathway•MIF acts as a transcriptional regulator under hypoxia
SummaryDegenerative cartilage endplate (CEP) shows decreased chondrification and increased ossification. Cartilage endplate stem cells (CESCs), with the capacity for chondro-osteogenic differentiation, are responsible for CEP restoration. CEP is avascular and hypoxic, while the physiological hypoxia is disrupted in the degenerated CEP. Hypoxia promoted chondrogenesis but inhibited osteogenesis in CESCs. This tissue-specific differentiation fate of CESCs in response to hypoxia was physiologically significant with regard to CEP maintaining chondrification and refusing ossification. MIF, a downstream target of HIF1A, is involved in cartilage and bone metabolisms, although little is known about its regulatory role in differentiation. In CESCs, MIF was identified as a key point through which HIF1A regulated the chondro-osteogenic differentiation. Unexpectedly, unlike the traditionally recognized mode, increased nuclear-expressed MIF under hypoxia was identified to act as a transcriptional regulator by interacting with the promoter of SOX9 and RUNX2. This mode of HIF1A/MIF function may represent a target for CEP degeneration therapy.
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