Yiting Kang

Osteoporosis is highly prevalent in postmenopausal women, causing chronic pain, fractures, and limited mobility that burden individuals and society. While resistance exercise benefits bone health, its role in osteoporotic bone injury healing and underlying mechanisms remain unclear. This study aimed to explore the effects of 10-week weight-bearing ladder climbing exercise on ovariectomy (OVX)-induced osteoporosis and subsequent bone injury healing, and to investigate whether these effects are associated with the myostatin (MSTN) and Wnt/β-catenin pathways. Fifty-four 12-week-old female SD rats were randomized into Sham, OVX, and OVX + EX groups. Rats in the OVX and OVX + EX groups underwent ovariectomy to induce postmenopausal osteoporosis, and those in the OVX + EX group received 10-week weight-bearing ladder climbing. After the exercise intervention, 6 rats in each group were sacrificed; the remaining rats underwent femoral midshaft drilling to establish bone injury. The improvement in osteoporosis was evaluated via Micro-CT, biomechanical tests, RT-qPCR for mRNA detection, and Western blot for measuring protein levels of MSTN and Wnt/β-catenin pathway-related molecules at post-exercise and 21 days post-injury. Bone healing was reflected by the bone volume fraction at the bone injury site detected via Micro-CT at 10 and 21 days post-injury. This exercise significantly enhanced muscle strength and improved femoral bone mineral density (BMD), trabecular microstructure, and biomechanical properties in OVX rats. Meanwhile, the level of MSTN in the OVX + EX group was decreased, the expression of its downstream signaling pathways was inhibited, and the mRNA and protein expressions of Wnt/β-catenin were upregulated. Moreover, 21 days after exercise intervention, the biomechanical properties and bone microstructure of the OVX + EX group were still significantly superior to those of the OVX group, and the aforementioned molecular regulatory effect remained. In addition, pre-conducted exercise was able to promote increases in bone volume fraction at the bone injury site 10 and 21 days after drilling, which was conducive to bone injury healing. Ten-week weight-bearing ladder climbing ameliorates OVX-induced bone loss and promotes osteoporotic bone repair via regulating the MSTN/ActRIIB/Smad3 and Wnt/β-catenin pathways, providing evidence for exercise as a safe non-pharmacological intervention.

Postmenopausal women face increased risks of osteoporosis and cardiovascular diseases due to estrogen decline. This study investigated the effects of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) on bone microstructure and cardiovascular risk factors in ovariectomized (OVX) mice. Results showed that both exercise regimens improved blood lipid profiles and vascular structure, reducing systolic blood pressure (−11.81% and −10.89%) and undercarboxylated osteocalcin (ucOCN) levels (−52.14% and −52.05%). However, moderate-intensity exercise was more effective in enhancing bone mineral density (+82.38% and +45.02%) and microstructure recovery. No significant correlation was found between ucOCN and cardiovascular disease risk factors, such as lipid parameters, systolic blood pressure, and vascular wall thickness. This study suggests that both exercise intensities can mitigate cardiovascular risks in OVX mice, which is independent of OCN. MICT is superior for promoting osteoporosis recovery.

Aims: As the ovaries age and women transition to menopause and postmenopause, reduced estradiol levels are associated with anxiety and depression. Exercise contributes to alleviate anxiety and depression and the bone‐derived hormone osteocalcin has been reported to be necessary to prevent anxiety‐like behaviors. The aim of this study was to investigate the effects of exercise on anxiety behaviors in climacteric mice and whether it was related to osteocalcin.Methods: Menopausal mouse model was induced by intraperitoneal injection of 4‐vinylcyclohexene diepoxide (VCD). Open field, elevated plus maze, and light–dark tests were used to detect anxious behavior in mice. The content of serum osteocalcin was measured and its correlation with anxiety behavior was analyzed. BRDU and NEUN co‐localization cells were detected with immunofluorescence. Western blot was applied to obtain apoptosis‐related proteins.Results: The VCD mice showed obvious anxiety‐like behaviors and 10 weeks of treadmill exercise significantly ameliorated the anxiety and increased circulating osteocalcin in VCD mice. Exercise increased the number of BRDU and NEUN co‐localization cells in hippocampal dentate gyrus, reduced the number of impaired hippocampal neurons, inhibited the expression of BAX, cleaved Caspase3, and cleaved PARP, promoted the expression of BCL‐2. Importantly, circulating osteocalcin levels were positively associated with the improvements of anxiety, the number of BRDU and NEUN co‐localization cells in hippocampal dentate gyrus and negatively related to impaired hippocampal neurons.Conclusion: Exercise ameliorates anxiety behavior, promotes hippocampal dentate gyrus neurogenesis, and inhibits hippocampal cell apoptosis in VCD‐induced menopausal mice. They are related to circulating osteocalcin, which are increased by exercise.

During bone remodeling, high extracellular calcium levels accumulated around the resorbing bone tissue as soon as the activation of osteoclasts. However, if and how calcium is involved in the regulation of bone remodeling remains unclear. In this study, the effect of high extracellular calcium concentrations on osteoblast proliferation and differentiation, intracellular calcium ([Ca²⁺]_i) levels, metabolomics, and the expression of proteins related to energy metabolism were investigated. Our results showed that high extracellular calcium levels initiated a [Ca²⁺]_i transient via the calcium-sensing receptor (CaSR) and promoted the proliferation of MC3T3-E1 cells. Metabolomics analysis showed that the proliferation of MC3T3-E1 cells was dependent on aerobic glycolysis, but not the tricarboxylic acid cycle. Moreover, the proliferation and glycolysis of MC3T3-E1 cells were suppressed following the inhibition of AKT. These results indicate that calcium transient triggered by high extracellular calcium levels activated glycolysis via AKT-related signaling pathways and ultimately promoted the proliferation of osteoblasts.