Effects of treadmill exercise on bone and skeletal muscle in ovariectomized rats through Wnt/β-catenin pathway

Physical exercise has been reported positive effects on both bones and muscles simultaneously. The underlying mechanisms remain unclear. This study investigated whether treadmill training can inhabit bone loss and muscle atrophy in ovariectomized (OVX) rats by activating Wnt/β-Catenin pathway.

8-week-old female Sprague-Dawley (SD) rats were randomly divided into three groups (n = 12 per group): Sham group with sham operation, OVX group with bilateral ovariectomy and sham treadmill training, and ET groups with bilateral ovariectomy and 12 weeks treadmill training. Bone mineral density/microarchitecture, level of serum biochemical markers, osteogenesis-related and muscle atrophy markers, and Wnt/β-catenin signaling genes in rat were then analyzed.

The 12-week treadmill training intervention showed a significant effect on inhibition of ovariectomy-induced bone loss and muscle atrophy. Further analysis revealed that treadmill training enhanced bone mineral density of the proximal femoral metaphysis, improved the proximal tibia microarchitecture, inhabiting bone marrow adipogenesis, decreased serum TRACP-5b, CTX-I, CK, LDH and MDA levels, and elevated the serum BALP, Irisin, CAT and SOD levels. Furthermore, treadmill training upregulated RUNX2, BMP2 and Osterix, but downregulated PPAR-γ in the bone marrow of OVX rats; it downregulated atrogin1 and MuRF1, but upregulated PAX7, in their skeletal muscle; additionally, it markedly upregulated Wnt3a, LRP5 and β-catenin, but downregulated DKK1 and GSK3β, in both their bone marrow and skeletal muscle tissues.

Treadmill training mitigates bone loss and muscle damage associated with estrogen deficiency. The Wnt/β-catenin signaling pathway potentially serves as a common mechanism.