Figure legend
Figure 1 Study design and timeline. The rats were injected with
monosodium iodoacetate to induce an osteoarthritis (OA) model. In
experiment 1: The rats were randomly divided into a control group, an OA
group and an OA+HIIT group (N= 12/group). Control rats received an
intraarticular injection of an equal volume of normal saline. HIIT was
conducted in the fourth week and consecutively exercised for six weeks.
In experiment 2: OA rats were randomly divided into the OA group,
OA+HIIT group, OA+ C-A1 group and OA+ C-A1+HIIT group (N= 12/group). In
the third week of the OA model, rats were given an intraperitoneal
injection of C-A1 to activate the Jak2/Stat3 pathway, followed by HIIT
intervention in the fourth week.
Figure 2 Body weight and pain threshold of rats in each group.
A: Changes in body weight after MIA injection into the right knee of
control rats, OA rats, and OA+HIIT rats. N=6/ group, two-way repeated
measures ANOVA with Tukey and Bonferroni tests as post hoc tests. B: The
von Frey method measured the Mechanical withdrawal threshold (MWT). N=6/
group, repeated measures ANOVA with Tukey and Bonferroni tests as post
hoc tests. **P < 0.01, ***P < 0.001.
C: Changes in body weight after MIA injection into the right knee of OA
rats, OA+HIIT rats, OA+ C-A1 rats, and OA+ C-A1+HIIT rats. N=6/ group,
two-way repeated measures ANOVA with Tukey and Bonferroni tests as post
hoc tests. D: The von Frey method measured the Mechanical withdrawal
threshold (MWT). N=6/ group, repeated measures ANOVA with Tukey and
Bonferroni tests as post hoc tests. *P < 0.05,
***P < 0.001.
Figure 3 HIIT reversed the osteoarthritis (OA)-induced
inflammatory response. A: The content levels of SP and IL-6 in the serum
of rats. N=6, one-way ANOVA, *P < 0.05, ***P < 0.001. B-C: Representative immunohistochemical images and
quantitative analysis of MMP-13 and IL-6 in the extracellular matrix,
blue is the nucleus, brown is target protein expression, scale =100 μm.
One-way ANOVA, *P < 0.05, **P < 0.01,
***P < 0.001.
Figure 4 HIIT drove the pheno-typic transformations of
microglia and down-regulated pain factors. A: The representative images
of immunofluorescence in the microglia (blue is denoted for the nucleus
and gold is for Tmem119 protein; scale bar = 100 µm) and quantitative
analysis of Tmem119. N = 6 each group, ***P < 0.001. B:
Flow cytometry analysis and quantification of CD68 and CD163 in
microglia. N= 6 each group, **P < 0.01. C:
Representative western blotting images of Glu, c-fos, SP, and IL-6, and
quantification. N= 6 each group. One-way ANOVA, *P <
0.05, **P < 0.01, ***P < 0.001.
Figure 5 The quantitative technique of protein mass
spectrometry and KEGG pathway analysis. The protein sequencing approach
was used to map the transcriptome of OA and OA+HIIT rats. (A) Heat map
of the differentially expressed genes. (B) Protein-protein interaction
(PPI) network shows the interactions among different proteins. (C-D) The
top 20 KEGG pathways were enriched between OA and OA-HIIT groups. (E)
The differentially expressed genes were shown in the volcano plot, with
red denoted for up-regulation and blue for down-regulation. (F) The main
proteins involved in Jak2/Stat3 signalling pathway were analyzed by
qRT-PCR. N= 6 each group. *P < 0.05 vs. OA.
Figure 6 HIIT promoted the pheno-typic transformations of
microglia and relieved pain in OA rats through Jak2/STAT3 pathway. A-B:
Flow cytometry analysis and quantification of CD68 and CD163 in
microglia. N = 6 each group. ***P < 0.001. C:
Representative western blotting images of Glu, c-fos, SP, and IL-6, and
quantification. N = 6 each group. *P < 0.05,
**P < 0.01.