title: MIF Plays a Key Role in Regulating Tissue-Specific Chondro-Osteogenic Differentiation Fate of Human Cartilage Endplate Stem Cells under Hypoxia.
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.
authors: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors: Yuan
authors: Y
authors: Yao
authors: Department of Neurobiology, College of Basic Medical Sciences, Third Military Medical University, Chongqing 400038, China.
authors: Qiyue
authors: Q
authors: Deng
authors: Department of Ophthalmology, Southwest Hospital, Third Military Medical University, Chongqing 400038, China.
authors: Weilin
authors: W
authors: Song
authors: Department of Stomatology, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors: Huiyu
authors: H
authors: Zhang
authors: Department of Orthopedics, General Hospital of Xizang Military Region of PLA, Lasa 850003, China.
authors: Yuanjing
authors: Y
authors: Li
authors: Department of Cardiology, Daping Hospital, Third Military Medical University, Chongqing 400042, China.
authors: Yang
authors: Y
authors: Yang
authors: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors: Xin
authors: X
authors: Fan
authors: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors: Minghan
authors: M
authors: Liu
authors: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors: Jin
authors: J
authors: Shang
authors: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors: Chao
authors: C
authors: Sun
authors: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China.
authors: Yu
authors: Y
authors: Tang
authors: Department of Orthopedics, The 422nd Hospital of PLA, Zhanjiang 524009, China.
authors: Xiangting
authors: X
authors: Jin
authors: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. Electronic address: 20016040@163.com.
authors: Huan
authors: H
authors: Liu
authors: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. Electronic address: bighuang2000@hotmail.com.
authors: Bo
authors: B
authors: Huang
authors: Department of Orthopedics, Xinqiao Hospital, Third Military Medical University, Chongqing 400037, China. Electronic address: happyzhou@vip.163.com.
authors: Yue
authors: Y
authors: Zhou
mesh_terms: D002356:Cartilage / Q000166:cytology*; D002454:Cell Differentiation / Q000235:genetics; D015687:Cell Hypoxia / Q000235:genetics; D002467:Cell Nucleus / Q000378:metabolism; D020219:Chondrogenesis / Q000235:genetics; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000378:metabolism*; D008263:Macrophage Migration-Inhibitory Factors / Q000378:metabolism*; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D008954:Models, Biological; D009045:Motor Endplate / Q000166:cytology*; D009928:Organ Specificity; D010012:Osteogenesis / Q000235:genetics; D011401:Promoter Regions, Genetic / Q000235:genetics; D055758:SOX9 Transcription Factor / Q000235:genetics; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism
chemical_list: D050659:Core Binding Factor Alpha 1 Subunit; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D008263:Macrophage Migration-Inhibitory Factors; D055758:SOX9 Transcription Factor; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human