Vagotomy accelerates the onset of symptoms during early disease progression and worsens joint-level pathogenesis in a male rat model of chronic knee osteoarthritis

Figures

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  Fig. 1. Summary of experimental design.

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  Fig. 2. Representative histological sections (10 ​μm) showing A) non-VGX and B) VGX knee joints. Features of joint remodeling in the OA knee are shown by C) cartilage thickness along the medial tibial plateau and D) bone area ratio (the ratio of trabecular bone area to total epiphyseal area). For C, an x-axis value of 0% corresponds to the interior aspect (corresponding with the left sides of Fig. 2A and B) of the medial condyle, while a value of 100% indicates the medial margin (corresponding with the right sides of Fig. 2A and B) of the same medial condyle. The representative sections of figures A and B are represented in figure C by a dashed line with the label “A” and “B”, respectively. Similarly, the representative sections of figures A and B are represented in figure D by a dashed square with the label “A” and “B”, respectively. Error bands/bars represent a 95% confidence interval.

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  Fig. 3. Gait balance and symmetry results for both groups. A) stance time imbalance of the hind limb (0% dashed line indicates equal stance times between the non-OA and OA limbs), B) spatial symmetry (50% dashed line indicates a foot strike of the OA limb placed halfway between two foot strikes of the non-OA limb), and C) temporal symmetry (50% dashed line indicates a foot strike of the OA limb occurring halfway between two foot strikes of the non-OA limb in time). A # indicates a significant shift (p ​< ​0.05), while a ∗ indicates a near-significant shift (0.05 ​< ​p ​< ​0.1) from the horizontal control (dashed) line. Error bars represent a 95% confidence interval.

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  Fig. 4. Individual stance times and peak vertical force for both groups. A) percent stance time of the OA limb, B) percent stance time of the non-OA limb, and C) peak vertical force as a percentage of body weight for the OA limb of both groups. Linear regression lines represent the predicted mixed-effect models for each group at a specific week. Individual points represent raw data. All error bands represent a 95% confidence interval.

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  Fig. 5. Tactile sensitivity measured via 50% paw withdrawal thresholds of the A) OA limb and B) non-OA limb across time for both groups. Individual points represent raw data, while filled points represent group means. All error bands represent a 95% confidence interval.

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  Fig. 6. Changes in gene expression (2−ΔΔCT) for limb-innervating (lumbar 3–5) dorsal root ganglia ipsilateral to the OA limb. A value of zero indicates equal expression between both groups; a value greater or less than zero corresponds with upregulation or downregulation of genes relative to non-VGX animals, respectively. Individual shapes correspond to the same animal across all genes, while filled point represented the mean. Bars represent the 95% confidence interval. For CGRP, the 95% confidence interval was too small (±0.43) to be represented.