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. Author manuscript; available in PMC: 2021 Mar 1.
Published in final edited form as: J Bone Miner Res. 2019 Dec 12;35(3):550–570. doi: 10.1002/jbmr.3908

Figure 1: Loss of MCT4 Causes Age-related Intervertebral Disc Degeneration.

Figure 1:

A-A") Representative immunohistochemical images showing MCT4-positive cells (red arrows) and MCT4-negative cells (blue arrows) in healthy (A), mid-degenerate (A'), and severe degenerate (A") human samples (Scale bar = 50 μm). B) Percent MCT4 immunopositivity in healthy, moderately-, and severely- degenerate human discs. C, C”) Safranin-O/Fast Green staining of the intervertebral disc in 8 mo WT and global MCT4 KO mice (Scale bar = 200 μm). D) Histological grade of degeneration using modified-Thompson grading scale. E) Average grade of NP and AF degeneration. F) Average grade of CEP degeneration using modified-Boos scale. G, G’) Average aspect ratio of NP compartment and percent of discs with abnormally reduced aspect ratio. (n= 3 discs/ animal; 4 animals/ genotype;). H, H') Safranin-O/Fast Green staining of the disc in 14 mo WT and MCT4 KO mouse disc (Scale bar= 200 μm). (I, I’) High magnification view of NP compartment shows vacuolated cells (yellow arrows) and proteoglycan-rich matrix (red arrows) in WT animals and NP cell fragmentation (green arrows) and fibrotic matrix deposition (blue arrows) in MCT4 KO animals. (J,J’) High magnification view of AF compartment shows organized lamellae (red arrows) in WT animals and disorganized, mucinous lamellae (blue arrows) in MCT4 KO animals. (K, K’) High magnification view of CEP/BEP compartment shows articular chondrocytic cells (yellow arrows) and organized, ossified matrix (red arrows) in WT animals and hypertrophic chondrocytes (green arrows) and cartilaginous templates (blue arrows) in MCT4 KO animals. (Scale bars= 50 μm). L) Histological grade of degeneration using modified-Thompson grading scale. M-O) Average modified-Thompson grade of NP and AF degeneration on average and by disc level. P, P’) Average grade of CEP degeneration using modified-Boos scale and percent of discs showing persistent cartilaginous template in CEP/BEP region. Q, Q') Average aspect ratio of NP compartment and percent of discs with abnormally reduced aspect ratio in the NP compartment. (n=3 discs/ animal; 8 animals/ genotype). Statistical analysis on non-parametric human data was performed by Kruskall Wallis and Connover Ingman post hoc test * p-value ≤ 0.05. Statistical analysis on mouse data: t-test, One-way ANOVA. n.s.= not significant; *, p-value ≤ 0.05; **, p-value ≤ 0.01; ***, p-value ≤ 0.001.