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Stem Cell Reports. 2016 Aug 9;7(2):249-62. doi: 10.1016/j.stemcr.2016.07.003.

MIF Plays a Key Role in Regulating Tissue-Specific Chondro-Osteogenic Differentiation Fate of Human Cartilage Endplate Stem Cells under Hypoxia.

Author information

1
Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
2
Department of Neurobiology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China.
3
Department of Ophthalmology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
4
Department of Stomatology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
5
Department of Orthopedics, General Hospital of Xizang Military Region of PLA, Lasa 850003, China.
6
Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
7
Department of Orthopedics, The 422nd Hospital of PLA, Zhanjiang 524009, China.
8
Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. Electronic address: 20016040@163.com.
9
Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. Electronic address: bighuang2000@hotmail.com.
10
Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. Electronic address: happyzhou@vip.163.com.

Abstract

Degenerative 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.

PMID:
27509135
PMCID:
PMC4982989
DOI:
10.1016/j.stemcr.2016.07.003
[Indexed for MEDLINE]
Free PMC Article

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