Published online Apr 18, 2024. doi: 10.5312/wjo.v15.i4.363
Peer-review started: November 22, 2023
First decision: January 24, 2024
Revised: February 4, 2024
Accepted: March 19, 2024
Article in press: March 19, 2024
Published online: April 18, 2024
Processing time: 144 Days and 0.3 Hours
Regular physical activity during childhood and adolescence is beneficial to bone development, as evidenced by the ability to increase bone density and peak bone mass by promoting bone formation.
To investigate the effects of exercise on bone formation in growing mice and to investigate the underlying mechanisms.
20 growing mice were randomly divided into two groups: Con group (control group, n = 10) and Ex group (treadmill exercise group, n = 10). Hematoxylin-eosin staining, immunohistochemistry, and micro-CT scanning were used to assess the bone formation-related indexes of the mouse femur. Bioinformatics analysis was used to find potential miRNAs targets of long non-coding RNA H19 (lncRNA H19). RT-qPCR and Western Blot were used to confirm potential miRNA target genes of lncRNA H19 and the role of lncRNA H19 in promoting osteogenic differentiation.
Compared with the Con group, the expression of bone morphogenetic protein 2 was also significantly increased. The micro-CT results showed that 8 wk moderate-intensity treadmill exercise significantly increased bone mineral density, bone volume fraction, and the number of trabeculae, and decreased trabecular segregation in the femur of mice. Inhibition of lncRNA H19 significantly upregulated the expression of miR-149 and suppressed the expression of markers of osteogenic differentiation. In addition, knockdown of lncRNA H19 significantly downregulated the expression of autophagy markers, which is consistent with the results of autophagy-related protein changes detected in mouse femurs by immunofluorescence.
Appropriate treadmill exercise can effectively stimulate bone formation and promote the increase of bone density and bone volume in growing mice, thus enhancing the peak bone mass of mice. The lncRNA H19/miR-149 axis plays an important regulatory role in osteogenic differentiation.
Core Tip: Adolescence is a critical period for laying the foundation for optimal peak bone mass in adulthood. Studies have shown that pre-puberty and early puberty are the periods when bones are most responsive to mechanical loading. It is essential to explore the effect of exercise on promoting bone formation in adolescence and its underlying mechanisms. In this paper, we explored the promotional effects of treadmill exercise on bone formation in growing mice and further explored the underlying mechanisms. Our results validate that moderate intensity running exercise is effective in stimulating bone formation and promoting increases in bone mineral density and bone mass, thereby enhancing peak bone mass in growing mice. Notably, the long non-coding RNA H19 (lncRNA H19)/microRNA-149 (miR-149) axis plays an important regulatory role in the osteogenic differentiation of bone mesenchymal stem cells. Overall, this paper emphasizes that exercise may promote bone formation in mice through the lncRNA H19/miR-149 axis, which may be closely related to the activation of autophagy.