A Rat Tail Temporary Static Compression Model Reproduces Different Stages of Intervertebral Disc Degeneration with Decreased Notochordal Cell Phenotype

作者：Hirata Hiroaki; Yurube Takashi^*; Kakutani Kenichiro; Maeno Koichiro; Takada Toru; Yamamoto Junya; Kurakawa Takuto; Akisue Toshihiro; Kuroda Ryosuke; Kurosaka Masahiro; Nishida Kotaro

来源：Journal of Orthopaedic Research, 2014, 32(3): 455-463.

DOI：10.1002/jor.22533

• intervertebral disc degeneration
• notochordal cell phenotype
• apoptotic cell death
• animal model
• spine

The intervertebral disc nucleus pulposus (NP) has two phenotypically distinct cell typesnotochordal cells (NCs) and non-notochordal 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 1.3MPa 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 2-1 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.

• 出版日期2014-3