Age‐related spontaneous lumbar intervertebral disc degeneration in a mouse model

Abstract

The pathogenesis of intervertebral disc degeneration is unclear, but it is a major cause of several spinal diseases. Animal models have historically provided an appropriate benchmark for understanding the human spine. However, there is little information about when intervertebral disc degeneration begins in the mouse or regarding the relationship between magnetic resonance imaging and histological findings. The aim for this study was to obtain information about age-related spontaneous intervertebral disc degeneration in the mouse lumbar spine using magnetic resonance imaging and a histological score regarding when the intervertebral disc degeneration started and how rapidly it progressed, as well as how our histological score detected the degeneration. The magnetic resonance imaging index yielded a moderate correlation with our Age-related model score. The Pfirrmann grade and magnetic resonance imaging index had moderate correlations with age. However, our Age-related model score had a high correlation with age. Intervertebral disc level was not a significant variable for the severity of disc degeneration. Both Pfirrmann grade and the Age-related model score were higher in the ≥14-month-old group than in the 6-month-old group. The present results indicated that mild but significant intervertebral disc degeneration occurred in 14-month-old mice, and the degree of degeneration progressed slowly, reaching a moderate to severe condition for 22-month-old mice. At least a 14-month follow-up is mandatory for evaluating spontaneous age-related mouse intervertebral disc degeneration. The histological classification score can precisely detect the gradual progression of age-related spontaneous intervertebral disc degeneration in the mouse lumbar spine, and is appropriate for evaluating it. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 36:224-232, 2018.

Comparison of inbred mouse strains shows diverse phenotypic outcomes of intervertebral disc aging

“…BL6, LG/J and SM/J discs showed different tissue and cellular organization with aging. Interestingly, BL6 caudal discs showed little increase in degeneration grades with aging as reported for lumbar and cervical spine (Ohnishi et al, 2018). This is not surprising as in humans, prevalence of disc degeneration is higher at lumbar L5/S1 and cervical C5/C6 than the other levels, suggesting that factors such as the local mechanical environment could play an important role in increasing the susceptibility to degeneration (Teraguchi et al, 2014).…”

“…While disc degeneration is complex and thought to have contributions from a multiple factors, aging is considered one of the major risk factors (Novais et al, 2019; Ohnishi et al, 2018). Human disc degeneration has diverse phenotypes ranging from loss of disc height, herniations and disc calcification (Cheung et al, 2009); however, the contribution of genetic background to these aging phenotypes is not well understood.…”

“…BL6 mice are considered gold‐standard model for aging studies and are widely used to characterize the aging of the spine (Novais et al, 2019; Ohnishi et al, 2018). It is well known that human disc aging and degeneration comprises a wide spectrum of phenotypes, many of which are not recapitulated in the BL6 model, that is disc calcification (Chanchairujira et al, 2007; Cheung et al, 2009).…”

“…This is becoming more important as increasing lifespan is contributing to a rise in age‐dependent diseases. It is known that over the course of lifespan, discs experience decreased levels and quality of extracellular matrix proteins, compromised biomechanical properties, increase in inflammatory cytokine expression, catabolic processes and cell death (Caldeira et al, 2017; Ohnishi, Sudo, Tsujimoto, & Iwasaki, 2018). Similarly, senescence, herniations and calcifications have been correlated with degenerative phenotypes in the disc (Novais, Diekman, Shapiro, & Risbud, 2019).…”

Cell properties of nucleus pulposus progenitor cells declines with intervertebral disc degeneration

“…The tissue microenvironment is still thought to play an important role in maintaining SC proliferation and differentiation [29,30]. In addition, cell properties decrease with age and degeneration during IDD progression [31]. Thus, the present study was performed to assess changes in the biological characteristics and regeneration potential of NPPCs from different IVD state.…”