New In Vivo Animal Model to Create Intervertebral Disc Degeneration and to Investigate the Effects of Therapeutic Strategies to Stimulate Disc Regeneration

Kroeber, Markus; Unglaub, Frank; Wang, Haili; Schmid, Carsten; Thomsen, M.; Nerlich, Andreas; Richter, Wiltrud

doi:10.1097/00007632-200212010-00007

Cited by 177 publications

(160 citation statements)

References 20 publications

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“…All animals of Comparison between the control group N (number N1-N5), the compression group (C1-C5) and the distraction group (D1-D3) this group showed lower intradiscal pressure when compared with N. Additionally, load application resulted in lower disc height in lateral radiograph, which verified disc compression and approximated the degree of disc degeneration. As reported earlier, morphology showed degenerative changes after 28 days of axial compression [10]. We believe that the IVD pressure decrease in compressed discs is consistent with earlier findings and support the concept of moderate disc degeneration.…”

Section: Discussionsupporting

confidence: 93%

“…Disc degeneration in animal models is still a matter of debate [1,[8][9][10][11][12][13]. Most studies with mechanically induced disc degeneration demonstrated a correlation between compression force and disc degeneration [1, 9, Fig.…”

Section: Discussionmentioning

confidence: 99%

“…Dorsal to the lumbar spine a custom-made external loading device was attached to the vertebra body L3 and L4 [10]. After the wound was closed, axial stress to the disc was immediately created by a calibrated spring within the loading device so as to produce an external disc compressive force of approximately 200 N. Postoperatively, all animals were allowed free unrestricted weight bearing and activity in cages.…”

Section: Surgical Procedures and The Ivd Pressure Measurementmentioning

confidence: 99%

“…The mechanism is an external application of controlled and far hyper-physiological axial compression to one lumbar spine disc [10,26]. Recently we reported that axial distraction could be a therapeutic option in degenerative disc disease [12].…”

mentioning

confidence: 99%

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Intradiscal pressure measurements in normal discs, compressed discs and compressed discs treated with axial posterior disc distraction: an experimental study on the rabbit lumbar spine model

et al. 2005

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Section: Discussionsupporting

confidence: 93%

Section: Discussionmentioning

confidence: 99%

Section: Surgical Procedures and The Ivd Pressure Measurementmentioning

confidence: 99%

mentioning

confidence: 99%

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Intradiscal pressure measurements in normal discs, compressed discs and compressed discs treated with axial posterior disc distraction: an experimental study on the rabbit lumbar spine model

et al. 2005

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“…Among many genetic and environmental factors that may contribute to the development of IVDD, disc cell death through apoptosis appears to be a major component (Ariga et al 2001(Ariga et al , 2003Court et al 2001;Gruber and Hanley 1998;Kohyama et al 2000;Kroeber et al 2002;Lotz and Chin 2000;Lotz et al 1998;Park et al 2001aPark et al ,b, 2005Park et al , 2006Rannou et al 2004;Walsh and Lotz 2004;Wang et al 2006a;Zhao et al 2006Zhao et al , 2007, but the signal transduction pathways involved in disc cell apoptosis have not been fully understood.…”

Section: Introductionmentioning

confidence: 99%

Both endoplasmic reticulum and mitochondria are involved in disc cell apoptosis and intervertebral disc degeneration in rats

Zhao

Zhang

Jiang

et al. 2009

AGE

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Intervertebral disc cell apoptosis occurs through either death receptor or mitochondrial pathway, but whether disc cell apoptosis is also mediated by the endoplasmic reticulum (ER) pathway remains unclear. The objective of this study was to investigate whether ER and mitochondria are co-involved in disc cell apoptosis and intervertebral disc degeneration (IVDD) in rats. Forty-eight rats were used for in vivo experiments. IVDD was characterized by X-ray and histomorphology examination, disc cell apoptosis was detected by TUNEL staining, and the co-involvement of ER and mitochondria in apoptosis was determined by immunohistochemical staining for GRP78, GADD153, caspase-12, and cytochrome C. Additional eight rats were used for annular cell isolation and culture. After sodium nitroprusside treatment, annular cell apoptosis was observed morphologically and quantified by flow cytometry; the expression of biomarkers of ER stress and mitochondrial dysfunction were analyzed by reverse transcriptase PCR (RT-PCR), fluorescence double labeling, and Western blot; and mitochondrial membrane potential was detected by 5′,6,6′-tetrachloro-1,1′,3,3′-tetraethylbenzimidazolcarbo cyanine iodide (JC-1) staining. Finally, NS3694 and Z-ATAD-FMK were employed to inhibit the formation of apoptosome complex and the activation of caspase-12, respectively, and apoptotic incidence and caspase-9 activity were assayed. We found that IVDD, induced by unbalanced dynamic and static forces in the rats, was accompanied by increased disc cell apoptosis and enhanced expression of GRP78, GADD153, caspase-12, and cytochrome C. Annular cell apoptosis induced by sodium nitroprusside was confirmed by morphologic observation and flow cytometry. With increased apoptosis, the expression of GRP78, GADD153, and caspase-12 upregulated, mitochondrial membrane potential decreased, and accumulation of cytochrome C in the cytosol manifested. Furthermore, NS3694 and Z-ATAD-FMK dramatically suppress annular cell apoptosis and caspase-9 activity. In conclusion, disc cell apoptosis mediated simultaneously by ER and mitochondria plays a potent role in IVDD.

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Exogenous crosslinking recovers the functional integrity of intervertebral disc secondary to a stab injury

Chuang

Lin

Tsai

et al. 2009

J Biomedical Materials Res

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Exogenous crosslinking was proved to improve the fatigue resistance of anulus fibrosus and the stability of motion segment. The effect of crosslinking on the recovery of stab-injured discs, however, was less studied. The purpose of this study is to find if the exogenous crosslinking can increase the mechanical function of injured discs. Fresh healthy porcine discs (T2/T9) from 6-month-old swine were obtained immediately following death. Anular puncture using 16 and 18 G spinal needle were used to create medium and large disc stab injury models. Three treatments were designed for each injury model. The first one is the injured discs without treatment. The second one is the injured discs soaked with phosphate buffered solution for 2 days. The third one is the injured discs soaked with 0.33% genipin solution for 2 days. The disc integrity was evaluated using quantitative discomanometry (QD) apparatus. Four QD parameters, that is, the leakage pressure and volume, and the saturate pressure and volume, were analyzed to find the efficacy of treatment. We found that soaking of genipin solution recovered the disc leakage pressure from 1.3 to 1.8 MPa in 16 G-injury-model and from 2.3 to 3.2 MPa in 18 G-injury-model, and recovered the saturate pressure from 1.6 to 2.0 MPa in 16 G-injury-model and from 2.7 to 3.7 MPa in 18 G-injury-model. The improvement of disc integrity by soaking with genipin solution indicate that the exogenous crosslinking may help the biomechanical performance of an injured disc.

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New In Vivo Animal Model to Create Intervertebral Disc Degeneration and to Investigate the Effects of Therapeutic Strategies to Stimulate Disc Regeneration

Cited by 177 publications

References 20 publications

Intradiscal pressure measurements in normal discs, compressed discs and compressed discs treated with axial posterior disc distraction: an experimental study on the rabbit lumbar spine model

Intradiscal pressure measurements in normal discs, compressed discs and compressed discs treated with axial posterior disc distraction: an experimental study on the rabbit lumbar spine model

Both endoplasmic reticulum and mitochondria are involved in disc cell apoptosis and intervertebral disc degeneration in rats

Exogenous crosslinking recovers the functional integrity of intervertebral disc secondary to a stab injury

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