期刊
INFLAMMATION
卷 46, 期 1, 页码 270-284出版社
SPRINGER/PLENUM PUBLISHERS
DOI: 10.1007/s10753-022-01732-y
关键词
Intervertebral disc degeneration; Hypoxia-inducible factor-1 alpha; Protective role; TNF-alpha; IVDD model
In this study, the effects of HIF-1 alpha on mouse primary nucleus pulposus cells (MNPCs) exposed to TNF-alpha were observed, the potential mechanism was explored and a rabbit IVDD model was established to verify the protective role of HIF-1 alpha on IVDD.
Intervertebral disc degeneration (IVDD) demonstrates a gradually increased incidence and has developed into a major health problem worldwide. The nucleus pulposus is characterized by the hypoxic and avascular environment, in which hypoxia-inducible factor-1 alpha (HIF-1 alpha) has an important role through its participation in extracellular matrix synthesis, energy metabolism, cellular adaptation to stresses and genesis. In this study, the effects of HIF-1 alpha on mouse primary nucleus pulposus cells (MNPCs) exposed to TNF-alpha were observed, the potential mechanism was explored and a rabbit IVDD model was established to verify the protective role of HIF-1 alpha on IVDD. In vitro results demonstrated that HIF-1 alpha could attenuate the inflammation, apoptosis and mitochondrial dysfunction induced by TNF-alpha in MNPCs; promote cellular anabolism; and inhibit cellular catabolism. In vivo results demonstrated that after establishment of IVDD model in rabbit, disc height and IVD extracellular matrix were decreased in a time-dependent manner, MRI analysis showed a tendency for decreased T2 values in a time-dependent manner and supplementation of HIF-1 alpha improved histological and imaginative IVDD while downregulation of HIF-1 alpha exacerbated this degeneration. In summary, HIF-1 alpha protected against IVDD, possibly through reducing ROS production in the mitochondria and consequent inhibition of inflammation, metabolism disorders and apoptosis of MNPCs, which provided a potential therapeutic instrument for the treatment of IVDD diseases.
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