scholarly journals Rat tail static compression model mimics extracellular matrix metabolic imbalances of matrix metalloproteinases, aggrecanases, and tissue inhibitors of metalloproteinases in intervertebral disc degeneration

2012 ◽  
Vol 14 (2) ◽  
pp. R51 ◽  
Author(s):  
Takashi Yurube ◽  
Toru Takada ◽  
Teppei Suzuki ◽  
Kenichiro Kakutani ◽  
Koichiro Maeno ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinases ◽  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Static Compression ◽  
Tissue Inhibitors ◽  
Compression Model ◽  
Rat Tail

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 ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Cell Phenotype ◽  
Static Compression ◽  
Notochordal Cell ◽  
Compression Model ◽  
Rat Tail

Static Compression Induces ECM Remodeling and Integrin α2β1 Expression and Signaling in a Rat Tail Caudal Intervertebral Disc Degeneration Model

Spine ◽  
2017 ◽  
Vol 42 (8) ◽  
pp. E448-E458 ◽  
Author(s):  
ZhanJun Yan ◽  
YouDong Pan ◽  
ShiHui Wang ◽  
MaoHua Cheng ◽  
HongMei Kong ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Static Compression ◽  
Ecm Remodeling ◽  
Rat Tail

scholarly journals Involvement of Autophagy in Rat Tail Static Compression-Induced Intervertebral Disc Degeneration and Notochordal Cell Disappearance

2021 ◽  
Vol 22 (11) ◽  
pp. 5648
Author(s):  
Takashi Yurube ◽  
Hiroaki Hirata ◽  
Masaaki Ito ◽  
Yoshiki Terashima ◽  
Yuji Kakiuchi ◽  
...  
Keyword(s):  
Intervertebral Disc ◽  
Disc Degeneration ◽  
Time Course ◽  
The Body ◽  
Terminal Deoxynucleotidyl Transferase ◽  
Autophagic Flux ◽  
Static Compression ◽  
Notochordal Cell ◽  
Notochordal Cells ◽  
Rat Tail

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.

scholarly journals JAG2/Notch2 inhibits intervertebral disc degeneration by modulating cell proliferation, apoptosis, and extracellular matrix

2019 ◽  
Vol 21 (1) ◽  
Author(s):  
Jun Long ◽  
Xiaobo Wang ◽  
Xianfa Du ◽  
Hehai Pan ◽  
Jianru Wang ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Extracellular Matrix ◽  
Cell Proliferation ◽  
Intervertebral Disc ◽  
Notch Signaling ◽  
Disc Degeneration ◽  
Intervertebral Disc Degeneration ◽  
Caspase 8 ◽  
Tnf Α ◽  
Intradiscal Injection

Abstract Background Intervertebral disc degeneration (IVDD)-related disorders are the major causes of low back pain. A previous study suggested that Notch activation serves as a protective mechanism and is a part of the compensatory response that maintains the necessary resident nucleus pulposus (NP) cell proliferation to replace lost or non-functional cells. However, the exact mechanism remains to be determined. In this study, we aimed to investigate the role of JAG2/Notch2 in NP cell proliferation and apoptosis. Methods Recombinant JAG2 or Notch2, Hes1, and Hey2 siRNAs were used to activate or inhibit Notch signaling. Cell proliferation, apoptosis, cell cycle regulatory factors, and pathways associated with Notch-mediated proliferation were examined. In vivo experiments involving an intradiscal injection of Sprague-Dawley rats were performed. Results Recombinant JAG2 induced Notch2 and Hes1/Hey2 expression together with NP cell proliferation. Downregulation of Notch2/Hes1/Hey2 induced G0/G1 phase cell cycle arrest in NP cells. Moreover, Notch2 mediated NP cell proliferation by regulating cyclin D1 and by activating PI3K/Akt and Wnt/β-catenin signaling. Furthermore, Notch signaling inhibited TNF-α-promoted NP cell apoptosis by suppressing the formation of the RIP1-FADD-caspase-8 complex. Finally, we found that intradiscal injection of JAG2 alleviated IVDD and that sh-Notch2 aggravated IVDD in a rat model. These results indicated that JAG2/Notch2 inhibited IVDD by modulating cell proliferation, apoptosis, and extracellular matrix. The JAG2/Notch2 axis regulated NP cell proliferation via PI3K/Akt and Wnt/β-catenin signaling and inhibited TNF-α-induced apoptosis by suppressing the formation of the RIP1-FADD-caspase-8 complex. Conclusions The current and previous results shed light on the therapeutic implications of targeting the JAG2/Notch2 axis to inhibit or reverse IVDD.

scholarly journals The Unwounded Skin Remodeling in Animal Models of Diabetes Types 1 and 2

2013 ◽  
pp. 519-526 ◽  
Author(s):  
M. KNAŚ ◽  
M. NICZYPORUK ◽  
A. ZALEWSKA ◽  
H. CAR
Keyword(s):  
Extracellular Matrix ◽  
Matrix Metalloproteinases ◽  
Diabetes Type ◽  
Tissue Inhibitor Of Metalloproteinase ◽  
Tissue Inhibitors Of Metalloproteinases ◽  
Control Group ◽  
Diabetes Type 1 ◽  
Tissue Inhibitors ◽  
The Matrix

Diabetes mellitus types 1 and 2 are chronic diseases that cause serious health complications, including dermatologic problems. The diabetic skin is characterized by disturbances in collagen metabolism. A tissue remodeling depends on the degradation of extracellular matrix through the matrix metalloproteinases, which are regulated by e.g. the tissue inhibitors of metalloproteinases. The balance between matrix metalloproteinases (MMPs) and tissue inhibitors of matrix metalloproteinases (TIMPs) is essential to maintain homeostasis in the skin. The aim of this study was to determine the concentration of metalloproteinase 2, tissue inhibitor of metalloproteinase 3 and the concentration of collagen type 1 in unwounded skin of diabetes type 1 and 2 and healthy controls. The treatment of diabetes resulted in a significant decrease of MMP2, increase of TIMP3 and COL1 concentrations in the skin as compared to the untreated diabetic skin. The concentrations of MMP2 in the skin of treated rats did not show significant differences from the healthy control group. TIMP3 concentrations in the skin of treated rats are not returned to the level observed in the control group. Disturbances of the extracellular matrix of the skin are similar in diabetes type 1 and 2. Application of insulin in diabetes therapy more preferably affects the extracellular matrix homeostasis of the skin.

Sign in / Sign up

Export Citation Format

Share Document