Treadmill training regulates β-catenin signaling through phosphorylation of GSK-3β in lumbar vertebrae of ovariectomized rats

Postmenopausal osteoporosis is associated with high level of adipogenesis within the bone marrow at the expense of osteoblast population. The mechanical effect on beta-catenin through phosphorylation of glycogen synthase kinase-3 beta (GSK-3 beta) is critical for inhibition of adipogenesis in mesenchymal stem cells in vitro. In present study, we hypothesized that treadmill training could regulate the beta-catenin signaling through phosphorylation of GSK-3 beta in the lumbar vertebrae of ovariectomized (OVX) rats. 3-month-old female Sprague-Dawley rats were divided randomly into the following four groups: (a) Sham, (b) OVX, (c) OVX exercised (EX), and (d) OVX estrogen replacement (E-2). At the end of the experiment, the serum levels of estradiol (E-2) and luteinizing hormone (LH), the ultimate lumbar vertebra strength, as well as the protein expression for peroxisome proliferators-activated receptor gamma (PPAR gamma), beta-catenin, P-GSK-3 beta, and osterix (Osx) in lumbar vertebrae were analyzed. Moreover, the protein expression for beta-catenin and P-GSK-3 beta were also examined in the uterus. The EX group had lower protein level of PPAR gamma, higher ultimate lumbar vertebral strength, and higher protein levels of beta-catenin, and P-GSK-3 beta in lumbar vertebral bodies compared with sedentary OVX group. The effects of EX treatment on the protein levels of beta-catenin and P-GSK-3 beta in bones were not reproducible in the uterus. Moreover, exercise treatment produced no estrogenic effect as evidenced by serum level of LH. In conclusion, this study suggested that treadmill training could activate the GSK-3 beta/beta-catenin signaling and inhibit the production of PPAR gamma in lumbar vertebrae of OVX rats, which may contribute to the prevention of bone loss in OVX rats.