scholarly journals A rat tail temporary static compression model reproduces different stages of intervertebral disc degeneration with decreased notochordal cell phenotype

2013 ◽  
Vol 32 (3) ◽  
pp. 455-463 ◽  
Author(s):  
Hiroaki Hirata ◽  
Takashi Yurube ◽  
Kenichiro Kakutani ◽  
Koichiro Maeno ◽  
Toru Takada ◽  
...  
2021 ◽  
Vol 22 (11) ◽  
pp. 5648
Author(s):  
Takashi Yurube ◽  
Hiroaki Hirata ◽  
Masaaki Ito ◽  
Yoshiki Terashima ◽  
Yuji Kakiuchi ◽  
...  

The intervertebral disc is the largest avascular low-nutrient organ in the body. Thus, resident cells may utilize autophagy, a stress-response survival mechanism, by self-digesting and recycling damaged components. Our objective was to elucidate the involvement of autophagy in rat experimental disc degeneration. In vitro, the comparison between human and rat disc nucleus pulposus (NP) and annulus fibrosus (AF) cells found increased autophagic flux under serum deprivation rather in humans than in rats and in NP cells than in AF cells of rats (n = 6). In vivo, time-course Western blotting showed more distinct basal autophagy in rat tail disc NP tissues than in AF tissues; however, both decreased under sustained static compression (n = 24). Then, immunohistochemistry displayed abundant autophagy-related protein expression in large vacuolated disc NP notochordal cells of sham rats. Under temporary static compression (n = 18), multi-color immunofluorescence further identified rapidly decreased brachyury-positive notochordal cells with robust expression of autophagic microtubule-associated protein 1 light chain 3 (LC3) and transiently increased brachyury-negative non-notochordal cells with weaker LC3 expression. Notably, terminal deoxynucleotidyl transferase dUTP nick end labeling-positive apoptotic death was predominant in brachyury-negative non-notochordal cells. Based on the observed notochordal cell autophagy impairment and non-notochordal cell apoptosis induction under unphysiological mechanical loading, further investigation is warranted to clarify possible autophagy-induced protection against notochordal cell disappearance, the earliest sign of disc degeneration, through limiting apoptosis.


Spine ◽  
2017 ◽  
Vol 42 (8) ◽  
pp. E448-E458 ◽  
Author(s):  
ZhanJun Yan ◽  
YouDong Pan ◽  
ShiHui Wang ◽  
MaoHua Cheng ◽  
HongMei Kong ◽  
...  

2017 ◽  
Vol 27 (1) ◽  
pp. 116-126 ◽  
Author(s):  
Qiuqian Wu ◽  
Jason H. Huang

OBJECTIVELumbar intervertebral disc degeneration, an age-related process, is a major cause of low-back pain. Although low-back pain is a very common clinical problem in the aging population, no effective treatment is available, largely owing to lack of understanding of the molecular mechanisms underlying disc degeneration. The goal of this study was to characterize how ectopic expression of Smurf2 driven by the collagen Type II alpha 1 (Col2a1) promoter alters disc cell phenotype and associated cellular events, matrix synthesis, and gene expression during disc degeneration in mice.METHODSTo characterize how ectopic expression of Smurf2 in Col2a1-promoter working cells affects the disc degeneration process, the authors performed histological and immunohistochemical analysis of lumbar spine specimens harvested from wild-type (WT) and Col2a1-Smurf2 transgenic mice at various ages (n ≥ 6 in each age group). To elucidate the molecular mechanism underlying Smurf2-mediated disc degeneration, the authors isolated cells from WT and Col2a1-Smurf2 transgenic lumbar intervertebral discs and performed Western blot and real-time RT-PCR (reverse transcription polymerase chain reaction) to examine the protein and mRNA levels of interesting targets.RESULTSThe authors demonstrated that approximately 30% of WT mice at 10–12 months of age had started to show disc degeneration and that the disc degeneration process was accelerated by 3–6 months in Col2a1-Smurf2 transgenic mice. Chondrocyte-like cell proliferation, maturation, and fibrotic tissue formation in the inner annulus were often accompanied by fibroblast-to-chondrocyte differentiation in the outer annulus in transgenic discs. The chondrocyte-like cells in transgenic discs expressed higher levels of connective tissue growth factor (CTGF) than were expressed in WT counterparts.CONCLUSIONSThe findings that ectopic expression of Smurf2 driven by the Col2a1 promoter accelerated disc degeneration in Col2a1-Smurf2 transgenic mice, and that higher levels of CTGF protein and mRNA were present in Col2a1-Smurf2 transgenic discs, indicate that Smurf2 accelerates disc degeneration via upregulation of CTGF.


2015 ◽  
Vol 15 (5) ◽  
pp. 1050-1059 ◽  
Author(s):  
Wei Yuan ◽  
Wu Che ◽  
Yun-Qi Jiang ◽  
Feng-Lai Yuan ◽  
Hui-Ren Wang ◽  
...  

2018 ◽  
Vol 24 ◽  
pp. 6456-6465 ◽  
Author(s):  
Tao Chen ◽  
Xiaofei Cheng ◽  
Jingcheng Wang ◽  
Xinmin Feng ◽  
Liang Zhang

Author(s):  
Xin Wang ◽  
Junhao Sun ◽  
Jianshi Tan ◽  
Pengzhong Fang ◽  
Jinlei Chen ◽  
...  

2012 ◽  
Vol 12 (9) ◽  
pp. S74
Author(s):  
Scott R. Montgomery ◽  
Hirokazu Inoue ◽  
Tuncay Kaner ◽  
Bayan G. Aghdasi ◽  
Yanlin Tan ◽  
...  

Author(s):  
A Lai ◽  
D H K Chow ◽  
W-S Siu ◽  
A D Holmes ◽  
F-H Tang ◽  
...  

Electroacupuncture (EA) has long been used as conservative treatment for low back pain (LBP). Its effect on relief of back pain has been demonstrated in many clinical studies. However, whether it has any effect on the biological properties of an intervertebral disc, which is one of the major causes of LBP, is still unclear. The aim of this study was, therefore, to investigate the effects of EA with different simulation frequencies on an intervertebral disc with simulated degeneration using an in-vivo rat-tail model. In this study, 33 rats were used. Disc degeneration was simulated in the rat caudal 8—9 disc via continuous static compressive loading of 11 N for 2 weeks. EA with a frequency of 2 or 100 Hz was then applied to the degenerated disc for 3 weeks with 3 sessions/week and 20 min/session. The intervertebral disc height was measured before and after compression as well as after EA intervention for 3 weeks. The static compression was found to result in a reduction in the disc height of about 22 per cent. There was no evidence that this change could be reversed after resting or the EA intervention. However, EA at 100 Hz was found to induce a further decrease in disc height, which was not shown for the rats after resting or EA at 2 Hz. The results of this study showed that effects of EA on disc degeneration are frequency dependent and adverse effects could result if EA at a certain frequency was used.


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