Bone Autophagy: A Potential Way of Exercise-Mediated Meg3/P62/Runx2 Pathway to Regulate Bone Formation in T2DM Mice

Abstract

Background Meg3 has been shown to attenuate T2DM bone autophagy by activating p62 to inhibit bone formation. However, whether exercise can reverse this process to promote T2DM bone formation and its mechanism remains unknown. Methods A T2DM mouse model was established by a high-fat diet and STZ injection, and the mice were trained with 8-week HIIT and downhill running exercise. Micro-CT was used to scan the bone microstructure. Bone morphology was observed by HE staining, and the osteoblast (OB) activity in bones was observed by AKP staining. Calcium ion and phosphorus concentration in serum was detected by ELISA; RT-PCR was used to detect the mRNA level, and Western blot was used to detect the protein level of related indexes in Meg3/p62/Runx2 pathway. Results The inhibition of bone autophagy, in the bones of T2DM mice, resulted in the degradation of the bone tissue morphology and structure, with the increase of the expressions of Meg3, PI3K, Akt, mTOR, p62 and NF-κB. However, 8-week HIIT and downhill running could reverse this process, especially downhill running, manifested with the up-regulation of miR-16 mRNA level, along with Beclin-1, LC3 II and Runx2 mRNA and protein level. Conclusion T2DM leads to pathology in model mice. Eight-week HIIT and downhill running exercise can inhibit Meg3, activate autophagy of osteoblasts and promote bone formation in T2DM mice.

The effects on type 2 diabetes mellitus mouse femoral bone achieved by anti-osteoporosis exercise interventions

“…Our results are in accordance with previous studies showing that HIIT with resistance training can significantly increase the BMD (69, 70). Eight weeks of HIIT and downhill running exercise mediated the Meg3/P62/Runx2 pathway to promote bone formation in T2DM mice (31). However, except for OSX, HIIT did not significantly improve the expression of RUNX2 and ALP compared with the T2DM+NE group.…”

“…RE was performed three times per week, with three climbs per session and five dynamic movements per climb (26). Group T2DM-HIIT mice underwent 8 weeks of HIIT, the speed of which was 16-26 m/min for 4 min with complete rest for 2 min, in a 10-round cycle, with warm-up and relaxation before and after exercise for 2 min (31). Mice in the T2DM-NE, T2DM-HIIT, T2DM-AE, T2DM-S, and T2DM-RE groups were kept on a HFD during the 8 weeks of exercise (Figure 1).…”

Piezo1‐mediated M2 macrophage mechanotransduction enhances bone formation through secretion and activation of transforming growth factor‐β1

“…41 We then established an in vivo running model using wild-type mice and showed that exercise increases bone mass. 42,43 However, little is known about how macrophages contribute to the mechanical force-induced osteogenesis of BMSCs. It has been determined that a crucial second messenger for macrophage polarization is Ca 2+ inward influx mediated by macrophage-sensitive ion channels.…”

“…Recent research has also demonstrated the advantages of exercise on M2 macrophage polarization and energy homeostasis 41 . We then established an in vivo running model using wild‐type mice and showed that exercise increases bone mass 42,43 . However, little is known about how macrophages contribute to the mechanical force‐induced osteogenesis of BMSCs.…”

Would Combination Be Better: Swimming Exercise and Intermittent Fasting Improve High-Fat Diet-Induced Nonalcoholic Fatty Liver Disease in Obese Rats via the miR-122-5p/SREBP-1c/CPT1A Pathway

“…All animals were adaptively fed for 1 week and then randomly divided into a normal control group (N, n=15) and an obesity model (n=60), respectively fed a normal chow diet 23 and a high-fat diet 24 (formulation in Table S1 ; purchased from Jiangsuxietong Pharmaceutical Bioengineering Co., Ltd. Nanjing, China) for 10 weeks. A body weight ≥20% of the average weight of the normal group was used as the criterion for obesity.…”