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. 2024 Apr 8;14(1):8176.
doi: 10.1038/s41598-024-58375-2.

Curcumin regulates autophagy through SIRT3-SOD2-ROS signaling pathway to improve quadriceps femoris muscle atrophy in KOA rat model

Hua Ye  1 , Yi Long  1 , Jia-Ming Yang  1 , Yan-Lin Wu  1 , Ling-Yan Dong  1 , Yan-Biao Zhong  1   2 , Yun Luo  3 , Mao-Yuan Wang  4   5
Affiliations

Curcumin regulates autophagy through SIRT3-SOD2-ROS signaling pathway to improve quadriceps femoris muscle atrophy in KOA rat model

Hua Ye et al. Sci Rep. .

Abstract

Knee osteoarthritis (KOA) usually leads to quadriceps femoris atrophy, which in turn can further aggravate the progression of KOA. Curcumin (CUR) has anti-inflammatory and antioxidant effects and has been shown to be a protective agent for skeletal muscle. CUR has been shown to have a protective effect on skeletal muscle. However, there are no studies related to whether CUR improves KOA-induced quadriceps femoris muscle atrophy. We established a model of KOA in rats. Rats in the experimental group were fed CUR for 5 weeks. Changes in autophagy levels, reactive oxygen species (ROS) levels, and changes in the expression of the Sirutin3 (SIRT3)-superoxide dismutase 2 (SOD2) pathway were detected in the quadriceps femoris muscle of rats. KOA led to quadriceps femoris muscle atrophy, in which autophagy was induced and ROS levels were increased. CUR increased SIRT3 expression, decreased SOD2 acetylation and ROS levels, inhibited the over-activation of autophagy, thereby alleviating quadriceps femoris muscle atrophy and improving KOA. CUR has a protective effect against quadriceps femoris muscle atrophy, and KOA is alleviated after improvement of quadriceps femoris muscle atrophy, with the possible mechanism being the reduction of ROS-induced autophagy via the SIRT3-SOD2 pathway.

Keywords: Autophagy; Curcumin; Knee osteoarthritis; Quadriceps femoris muscle.

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Conflict of interest statement

The authors declare no competing interests.

Figures

Figure 1
Figure 1
The schematic diagram of the experimental procedures. Gait analysis was performed the day before the Hulth procedure, 3 days after the procedure, and 35 days after the intervention. CUR treatment was started on the third day after the Hulth procedure, once a day for 35 days. Knee joints and quadriceps femoris muscle tissues were collected at the end of instillation and used for subsequent experiments.
Figure 2
Figure 2
CUR ameliorates gait abnormalities in rats caused by KOA. (A) Effect of KOA on the maximum contact area of rats. Maximum contact area (cm2) represents the maximum surface area of the claw in contact with the glass plate. (B) Effect of KOA on the mean intensity of rats. Mean intensity represents the average intensity of the claw in contact with the glass plate. (C) Effect of KOA on the swing of rats. Swing (s) is the time that the claw did not make contact with the glass plate during a walking cycle. (D) Effect of KOA on the stand of rats. Stand (s) is the time that the claw is in contact with the glass plate. (E) This is the print view of the claw on the glass plate. Control represents the blank control rats. Sham represents sham-operated group rats. KOA represents the knee osteoarthritis model group rats. KOA + CUR represents the treated group rats with feeding CUR. *P < 0.05, **P < 0.01, ***P < 0.001. All data are expressed as mean ± SD, n = 8 for each group.
Figure 3
Figure 3
Cartilage changes in each group of rats. (A) Gross morphological images of the rat knee joints. (B) H&E images of rat knee joints. Images were acquired at 100 ×, scale bars = 100 μm. Images were acquired at 200 ×, scale bars = 50 μm. (C) Images of Safranin O/Fast Green staining of rat knee joints. Images were acquired at 100 ×, scale bars = 100 μm. Images were acquired at 200 × , scale bars = 50 μm. (D) OARSI scores of rats in each group. Control represents the blank control rats. Sham represents sham-operated group rats. KOA represents the knee osteoarthritis model group rats. KOA + CUR represents the treated group rats with feeding CUR. ***P < 0.001, ****P < 0.0001 All data are expressed as mean ± SD, n = 3 for each group.
Figure 4
Figure 4
CUR can improve quadriceps femoris muscle atrophy due to KOA. (A) Representative H&E staining images of the quadriceps femoris muscle. Scale bar = 50 µm. (B) Myofiber CSA determined from cross-sections of the quadriceps femoris muscle. (C) Changes in MuRF-1 and Atrogin-1 expression were assessed by Western blotting. Equal protein loading was normalized by GAPDH. Original blots/gels were presented in Supplementary Figs. S1–S3. Control represents the blank control rats. Sham represents sham-operated group rats. KOA represents the knee osteoarthritis model group rats. KOA + CUR represents the treated group rats with feeding CUR. *P < 0.05, **P < 0.01, ***P < 0.001, **** P < 0.0001. All data are expressed as mean ± SD, n = 3 for each group.
Figure 5
Figure 5
Autophagy is hyperactivated in the quadriceps femoris muscle of KOA rats. (A) Changes in LC3 and P62 expression were assessed by Western blotting. Equal protein loading was normalized by GAPDH. Original blots/gels were presented in Supplementary Figs. S4–S6. *P < 0.05, **P < 0.01, ***P < 0.001. All data are expressed as mean ± SD, n = 3 for each group. (B) Abnormal morphology of autophagosomes and mitochondria in the quadriceps femoris muscle of KOA rats. Autophagosomes (red arrows). Images were acquired at 2500 × , scale bars = 5 μm. Images were acquired at 7000 × , scale bars = 2 μm. Control represents the blank control rats. Sham represents sham-operated group rats. KOA represents the KOA model group rats. KOA + CUR represents the treated group rats with feeding CUR.
Figure 6
Figure 6
CUR alleviates oxidative stress and inhibits autophagy via SIRT3-SOD2. (A) Protein expressions of SIRT3, SOD2, Ac-SOD2, LC3 and P62 was detected by western blotting. Equal protein loading was normalized by GAPDH. Original blots/gels were presented in Supplementary Figs. S7–S12. (B) ROS content in the quadriceps femoris muscle of rats in each group. (C) Activity of SOD2 in quadriceps femoris muscle of rats in each group. Control represents the blank control rats. Sham represents sham-operated group rats. KOA represents the knee osteoarthritis model group rats. KOA + CUR represents the treated group rats with feeding CUR. *P < 0.05, **P < 0.01, ***P < 0.001, ****P < 0.0001. All data are expressed as mean ± SD, n = 3 for each group.
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