Classification of Age-Related Changes in Lumbar Intervertebral Discs

Abstract

Histologic disc alterations can reliably be graded based on the proposed classification system providing a morphologic framework for more sophisticated molecular biologic analyses of factors leading to age-related disc changes. Diminished blood supply to the intervertebral disc in the first half of the second life decade appears to initiate tissue breakdown.

FOXO are required for intervertebral disk homeostasis during aging and their deficiency promotes disk degeneration

“…Four‐month‐old skeletally mature AcanCreER −/− ; Foxo1 fl/fl ; Foxo3 fl/fl ; and Foxo4 fl/fl (AcanCreER −/− ) and AcanCreER +/− ; Foxo1 fl/fl ; Foxo3 fl/fl ; and Foxo4 fl/fl (AcanCreER‐FOXO KO) mice were injected with tamoxifen, and FOXO expression was assessed 2 weeks later by qPCR analysis (Supporting information Figure S5 in Appendix S1). Unlike the results in the Col2a1‐Cre model, the reduction in FOXO expression upon tamoxifen administration in the AcanCreER model was more marked in the NP than in the AF, consistent with higher aggrecan expression in NP than in AF (Anderson & Tannoury, 2005; Boos et al, 2002; Kadow et al, 2015). Histopathological analysis revealed no differences in cellularity or disk height between genotypes at 6 months of age (Figure 3a–c).…”

“…As these developmental abnormalities could negatively impact the health of the IVD, we used the AcanCreER model to delete FOXO in skeletally mature mice. AcanCreER‐FOXO KO mice exhibited degenerative features that closely resembled the histological phenotype found in age‐related IDD characterized by a reduction in NP and EP cellularity, loss of NP/AF demarcation, and ossification of the EP (Alvarez‐Garcia, Matsuzaki, Olmer, Masuda, et al, 2017; Boos et al, 2002; Tam et al, 2017), but had no changes in the vertebral bodies. In addition, mice with conditional deletion of FOXO3 did not exhibit any IVD defects in postnatal growth or maturation but showed early onset of IDD with aging also characterized by a marked reduction in NP and EP cellularity, further supporting a critical role of FOXO in promoting mature IVD homeostasis by directly regulating cell survival.…”

“…The 4‐µm‐thick sagittal sections were stained with safranin O–fast green or picrosirius red staining for morphological analysis. Histological grading of NP/AF in mouse L4/L5 IVD was performed following the system described by Masuda et al (2005), and degenerative changes in EP were graded according to a modification to the scoring system described by Boos et al (2002). Briefly, the grading system in the NP and AF evaluated four different parameters: NP cellularity, border between NP and AF, matrix of the NP, and lamellar morphology in the AF.…”

“…The principal underlying causes of IDD are changes in cell numbers and phenotype and compromised biomechanical function in the IVD (Deyo & Weinstein, 2001). Aging is the major risk factor for IDD (Miller, Schmatz, & Schultz, 1988), and previous studies achieved substantial progress in describing age‐related changes in all IVD tissues, namely nucleus pulposus (NP), annulus fibrosus (AF), and endplates (EP) (Anderson & Tannoury, 2005; Boos et al, 2002; Kadow, Sowa, Vo, & Kang, 2015). Unlike any other connective tissues, age‐related changes in the IVD start early in life and involve a reduction in viable cells, particularly in the NP, and changes at the cellular and molecular level result in structural and functional impairment of the ECM, eventually leading to biomechanical failure and degeneration (Anderson & Tannoury, 2005; Kepler, Ponnappan, Tannoury, Risbud, & Anderson, 2013; Sivan, Wachtel, & Roughley, 2014; Vergroesen et al, 2015).…”

Molecular Basis of Intervertebral Disc Degeneration and Herniations: What Are the Important Translational Questions?

“…With aging, there is progressive reduction in the number of vascular channels in the vertebral EP [9]. These channels are the primary source of diffusion of nutrients into and waste products out of the intervertebral disc.…”