Table 2. Effects of surgery and spatial position on enzyme and inhibitor gene expression by mixed regression modelling of log-transformed expression data for each gene.
Gene | Model P | Effect of surgery | P | Effect of time after surgery as change per week | P | Effect of proximity to tarsus (T) or metarso-phalangeal joint (MTP) | P | Effect of distance (per cm) from midmetatarsus (lesion site) | P |
---|---|---|---|---|---|---|---|---|---|
ADAMTS4 | 0.10 | 0.98 (0.93–1.04) | 0.54 | MTP > T 0.76 (0.59–0.97) | 0.031 | 1.06 (0.96–1.17) | 0.22 | ||
0.20 | 0.82 (0.64–1.06) | 0.13 | 0.96 (0.90–1.03) | 0.28 | 0.86 (0.69–1.08) | 0.19 | 1.01 (0.93–1.10) | 0.84 | |
ADAMTS5 | <0.001 | 0.98 (0.93–1.03) | 0.44 | 1.15 (0.93–1.43) | 0.20 | ⬇ 0.76 (0.70–0.83) | <0.001 | ||
<0.001 | 0.94 (0.81–1.09) | 0.40 | 0.97 (0.91–1.03) | 0.27 | 1.16 (0.97–1.38) | 0.11 | ⬇ 0.73 (0.68–0.78) | <0.001 | |
MMP2 | 0.17 | 0.99 (0.85–1.15) | 0.88 | 0.72 (0.44–1.17) | 0.18 | ⬇ 0.81 (0.67–0.98) | 0.028 | ||
0.014 | 1.10 (0.76–1.61) | 0.60 | 0.99 (0.86–1.14) | 0.86 | 0.78 (0.53–1.16) | 0.21 | ⬇ 0.76 (0.66–0.89) | 0.001 | |
MMP9 | 0.20 | 0.92 (0.83–1.03) | 0.15 | 0.72 (0.49–1.07) | 0.11 | 0.95 (0.82–1.09) | 0.45 | ||
0.31 | 1.04 (0.80–1.34) | 0.79 | 0.93 (0.84–1.04) | 0.22 | 0.88 (0.64–1.20) | 0.42 | 0.90 (0.80–1.01) | 0.076 | |
MMP13 | <0.001 | 0.89 (0.80–0.99) | 0.039 | T > MTP 3.8 (2.0–7.6) | <0.001 | ⬇ 0.75 (0.57–0.97) | 0.031 | ||
<0.001 | ⬆ 20.0 (9.2–43.6) | <0.001 | ⬇ 0.86 (0.76–0.98) | 0.027 | T > MTP 2.9 (1.5–5.8) | 0.002 | ⬇ 0.39 (0.30–0.51) | <0.001 | |
TIMP1 | 0.35 | 0.97 (0.84–1.11) | 0.65 | 0.86 (0.56–1.32) | 0.49 | 0.86 (0.73–1.02) | 0.080 | ||
0.003 | ⬇ 0.57 (0.43–0.75) | <0.001 | 0.99 (0.85–1.15) | 0.88 | 1.07 (0.76–1.50) | 0.69 | 0.97 (0.85–1.10) | 0.66 | |
TIMP2 | <0.001 | 1.06 (0.93–1.26) | 0.37 | MTP > T 0.45 (0.26–0.76) | 0.003 | ⬇ 0.67 (0.54–0.82) | <0.001 | ||
<0.001 | ⬇ 0.38 (0.40–0.78) | <0.001 | 1.08 (0.93–1.26) | 0.33 | MTP > T 0.59 (0.37–0.94) | 0.028 | 0.84 (0.70–1.01) | 0.061 | |
TIMP3 | <0.001 | ⬆ 1.22 (1.11–1.34) | <0.001 | 0.81 (0.48–1.38) | 0.44 | 0.92 (0.75–1.14) | 0.45 | ||
<0.001 | ⬇ 0.56 (0.40–0.78) | 0.001 | ⬆ 1.22 (1.11–1.34) | <0.001 | 1.00 (0.67–1.50) | 0.99 | 1.04 (0.89–1.21) | 0.65 | |
GAPDH | 0.048 | 1.07 (1.00–1.14) | 0.037 | 0.96 (0.79–1.18) | 0.71 | 0.93 (0.86–1.01) | 0.073 | ||
<0.001 | ⬇ 0.73 (0.63–0.83) | <0.001 | 1.06 (0.99–1.14) | 0.10 | 1.01 (0.86–1.20) | 0.86 | 0.99 (0.93–1.05) | 0.71 |
Data was clustered by sheep and limb. For each gene, the results of the analysis in control tendons are listed first followed by results in transected tendons. Expression fold differences (as mean anti-log of beta-coefficients followed by the 95% confidence interval in parentheses) are given for models without transection (n = 129 observations; controls only) and with transection (n = 219; controls and operated) if model was significant (P<0.05) or one or more covariates was significant (P< 0.035 after Benjamini-Hochberg correction for false positives). Arrows indicate direction of change (increase or decrease).