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

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.