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

Abstract

The intervertebral disc nucleus pulposus (NP) has two phenotypically distinct cell types-notochordal cells (NCs) and nonnotochordal chondrocyte-like cells. In human discs, NCs are lost during adolescence, which is also when discs begin to show degenerative signs. However, little evidence exists regarding the link between NC disappearance and the pathogenesis of disc degeneration. To clarify this, a rat tail disc degeneration model induced by static compression at 1.3 MPa for 0, 1, or 7 days was designed and assessed for up to 56 postoperative days. Radiography, MRI, and histomorphology showed degenerative disc findings in response to the compression period. Immunofluorescence displayed that the number of DAPI-positive NP cells decreased with compression; particularly, the decrease was notable in larger, vacuolated, cytokeratin-8-and galectin-3-co-positive cells, identified as NCs. The proportion of TUNEL-positive cells, which predominantly comprised non-NCs, increased with compression. Quantitative PCR demonstrated isolated mRNA up-regulation of ADAMTS-5 in the 1-day loaded group and MMP-3 in the 7-day loaded group. Aggrecan-1 and collagen type 2a-1 mRNA levels were down-regulated in both groups. This rat tail temporary static compression model, which exhibits decreased NC phenotype, increased apoptotic cell death, and imbalanced catabolic and anabolic gene expression, reproduces different stages of intervertebral disc degeneration. ß

MMPs and ADAMTSs in intervertebral disc degeneration

“…In contrast, the expression of ADAMTS-1, ADAMTS-4, ADAMTS-5, ADAMTS-7, ADAMTS-12 and ADAMTS-15 is significantly increased in human degenerated IVD tissue compared with non-degenerated tissue [49,50]. In a rat tail disc degeneration model induced by static compression at 1.3 MPa, a significant increase in disc ADAMTS-4, ADAMTS-5, ADAMTS-7 and ADAMTS-12 mRNA levels is seen [51][52][53]. ADAMTS-5 levels in human herniated IVD tissue are also higher than those in normal IVD tissue [54].…”

Biological Responses of the Immature Annulus Fibrosus to Dynamic Compression in a Disc Perfusion Culture

“…However, because the NP, CEP and AF are structurally connected in both physiological and pathological situations, we deduced that investigations performed on a model that maintains the disc structure integrity may provide additional knowledge about the effects of mechanical stimuli on AF cells. Several rat or mouse tail models have been developed that totally preserve the disc integrity and provide a great deal of information on the cellular mechanobiology [Martin et al, 2013;Hirata et al, 2014]. However, because there are some differences in the compression patterns between rodent coccygeal discs and human lumbar discs [Wang et al, 2007;Beckstein et al, 2008], we did not perform this study on the rodent animal tail.…”

Responses and adaptations of intervertebral disc cells to microenvironmental stress: a possible central role of autophagy in the adaptive mechanism

“…The pathways involved in disc cell apoptosis induced by mechanical stress mainly include the mitochondrial and endoplasmic reticulum stress pathways (102,105,106). Static compression of 1.3 MPa on rat tail discs for 7 days could even reproduce the process of disc degeneration with the graduate loss of NC cells (107). In addition, dynamic and static compression both promoted the production of total ATP and lactate in porcine AF and NP cells, leading to decreased disc pH (108).…”

“…In addition, dynamic and static compression both promoted the production of total ATP and lactate in porcine AF and NP cells, leading to decreased disc pH (108). Following cell viability changes, the ECM and matrixdegrading enzyme could also be altered by loading changes (107,109). For example, human NP cells in tissue under dynamic compression for 2 h exhibited increased ADAMTS expression and decreased aggrecan expression (109).…”