Changes in the Nucleus Pulposus of the Intervertebral Disc in Bipedal Mice

Higuchi, Masanori; ABE, KAZUHIRO; KANEDA, KIYOSHI

doi:10.1097/00003086-198305000-00042

Cited by 39 publications

(26 citation statements)

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“…For instance, chondrodystrophoid dogs exhibit a loss of notochordal NP cells and are known to develop DDD, while their non-chondrodystrophoid counterparts retain these cells and generally avoid such disorders (Hunter et al, 2004a). Experimental procedures that compromise the notochordal NP likewise have adverse effects on disc health; both compressive loads that induce apoptosis and puncture injuries that lead to NP extrusion result in degenerative changes (Higuchi et al, 1983;Lotz et al, 1998;Lotz and Chin, 2000;Anderson et al, 2002;Hsieh et al, in press). Importantly, if we consider mechanically disrupted NP tissues as a scaled down version of the immature NP complete with physiologic cellular microenvironment, the results of hypoxic effects are consistent with the enhanced pro-chondrogenic, anti-notochordal phenotype observed in larger animals.…”

Section: Discussionmentioning

confidence: 99%

Environmental regulation of notochordal gene expression in nucleus pulposus cells

Rastogi

Thakore

Leung

et al. 2009

Journal Cellular Physiology

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Cells of the nucleus pulposus (NP) in the intervertebral disc are derived directly from the embryonic notochord. In humans, a shift in NP cell population coincides with the beginning of age-related changes in the extracellular matrix that can lead to spinal disorders. To begin identifying the bases of these changes, the manner by which relevant environmental factors impact cell function must be understood. This study investigated the roles of biochemical, nutritional, and physical factors in regulating immature NP cells. Specifically, we examined cell morphology, attachment, proliferation, and expression of genes associated with the notochord and immature NP (Sox9, CD24, and type IIA procollagen). Primary cells isolated from rat caudal discs were exposed to different media formulations and physical culture configurations either in 21% (ambient) or 2% (hypoxic) O2. As expected, cells in alginate beads retained a vacuolated morphology similar to chordocytes, with little change in gene expression. Interestingly, NP tissues not enzymatically digested were more profoundly influenced by oxygen. In monolayer, alpha-MEM preserved vacuolated morphology, produced the highest efficiency of attachment, and best maintained gene expression. DMEM and Opti-MEM cultures resulted in high levels of proliferation, but these appeared to involve small non-vacuolated cells. Gene expression patterns for cells in DMEM monolayer cultures were consistent with chondrocyte de-differentiation, with the response being delayed by hypoxia. Overall, results indicate that certain environmental conditions induce cellular changes that compromise the notochordal phenotype in immature NP. These results form the foundation on which the mechanisms of such changes can be elucidated.

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Section: Discussionmentioning

confidence: 99%

Environmental regulation of notochordal gene expression in nucleus pulposus cells

Rastogi

Thakore

Leung

et al. 2009

Journal Cellular Physiology

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“…While larger animals have been and continue to be used as degeneration models [8,12,18], the mouse is a particularly attractive animal because of its low housing costs, known genome for molecular bioassays, and the availability of transgenic animals whereby degenerative mechanisms can be studied through genetic alterations [7,[14][15][16]19,20]. Our laboratory recently completed a validation study in which the compression and torsion mechanical properties of mouse and rat motion segments were shown to compare well to human motion segment properties taken from the literature [4].…”

Section: Introductionmentioning

confidence: 99%

Mechanical differences between lumbar and tail discs in the mouse

Sarver

Elliott

2005

Journal Orthopaedic Research

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The mouse lumbar and tail discs are both used as models to study disc degeneration; however, the mechanical behavior of these two levels has not been compared. The objective of this study was to compare the elastic and viscoelastic mechanical properties of lumbar and tail discs of the mouse under axial compression-tension loading. We hypothesized that tail discs would have a larger transition zone (e.g., neutral zone) and would be less stiff in compression. To test these hypotheses, lumbar and tail bone-disc-bone motion segments were loaded in axial compression and tension. The nonlinear elastic mechanical behavior was examined using a tri-linear curvefit. Elastic behavior of lumbar and tail discs was most different in the low-stiffness transition region (neutral zone), where lumbar discs were nearly twice as stiff over half the axial displacement. In addition, viscoelastic behavior, which was examined using a stretchexponential curvefit, also showed large lumbar and tail differences, where lumbar discs compressed by 60% of their original height and tail discs by 98% after static creep compression. These results demonstrate that tail discs undergo far more axial displacement than lumbar discs under the same load. These findings are relevant to rodent tail models where chronic loads are applied in vivo to study mechanical pathways of degeneration. Furthermore, the tri-linear model, used here to curvefit the nonlinear compression-tension data, quantified stiffness in the transition zone for the first time, which may prove useful in future disc mechanical studies.

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“…9 -17 This cell plays a central role in the transition and ultimately comprises the major cell population of the mature or adult form of the fibrocartilaginous NP. 1,2,4,5,7,10,13,15,17,18 Thus, the chondrocyte-like cell is the most important cell type of the NP. It determines the initial state of the newly formed fibrocartilaginous NP and maintains it thereafter.…”

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confidence: 99%