A novel rat model of vertebral inflammation-induced intervertebral disc degeneration mediated by activating cGAS/STING molecular pathway.

A novel rat model of vertebral inflammation-induced intervertebral disc degeneration mediated by activating cGAS/STING molecular pathway.
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DOI:
10.1111/jcmm.16898
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发表时间:
2021-10
影响因子:
5.3
通讯作者:
Zhang Y
Zhang Y
中科院分区:
医学2区
文献类型:
--
作者:
Su Q;Cai Q;Li Y;Ge H;Zhang Y;Zhang Y;Tan J;Li J;Cheng B;Zhang Y

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In this study, we describe a new rat model of vertebral inflammation–induced caudal intervertebral disc degeneration (VI‐IVDD), in which IVD structure was not damaged and controllable segment and speed degeneration was achieved. VI‐IVDD model was obtained by placing lipopolysaccharide (LPS) in the caudal vertebral bodies of rats. Rat experimental groups were set as follows: normal control group, group with a hole drilled in the middle of vertebral body and not filled with LPS (Blank group), group with a hole drilled in the middle of vertebral body and filled with LPS (Mid group), and group with hole drilled in the vertebral body in proximity of IVD and filled with LPS (NIVD group). Radiological results of VI‐IVDD rats showed a significant reduction in the intervertebral space height and decrease in MRI T2 signal intensity. Histological stainings also revealed that the more the nucleus pulposus and endplate degenerated, the more the annulus fibrosus structure appeared disorganized. Immunohistochemistry analysis demonstrated that the expression of Aggrecan and collagen‐II decreased, whereas that of MMP‐3 increased in Mid and NIVD groups. Abundant local production of pro‐inflammatory cytokines was detected together with increased infiltration of M1 macrophages in Mid and NIVD groups. Apoptosis ratio remarkably enhanced in Mid and NIVD groups. Interestingly, we found a strong activation of the cyclic GMP‐AMP synthase /stimulator of interferon gene signalling pathway, which is strictly related to inflammatory and degenerative diseases. In this study, we generated a new, reliable and reproducible IVDD rat model, in which controllable segment and speed degeneration was achieved.
DOI: 10.1016/j.biomaterials.2017.03.013
发表时间: 2017-06
期刊: Biomaterials
影响因子: 14
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Bowles RD;Setton LA
通讯作者: Setton LA
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发表时间: 2018
影响因子: 7.3
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发表时间: 1991-10-01
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DOI: 10.1002/jbmr.4009
发表时间: 2020-08
期刊: Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research
影响因子: --
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Ashinsky BG;Bonnevie ED;Mandalapu SA;Pickup S;Wang C;Han L;Mauck RL;Smith HE;Gullbrand SE
通讯作者: Gullbrand SE
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