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Abstract
Estrogen deficiency frequently leads to a fall in estrogen receptor-α (ERα) numbers and then reduces the skeletal response to mechanical strain. It, however, is still unclear whether phytoestrogen administration will enhance the effects of exercise on the estrogen-deficient bone loss. This study aimed to determine the effect of Icariin treatment on the response of osteogenic formation to exercise in ovariectomized (OVX) rats. Thirty-two 3-month old female Sprague–Dawley rats were randomly allocated into four groups: (1) Sham-operated (SO); (2) OVX; (3) OVX plus exercise (EX); and (4) OVX plus exercise and Icariin (EI). After 8-week interventions, the rats were killed and samples were collected for bone morphometry, reverse transcription-polymerase chain reaction (RT-PCR), and Western blot analyses. EI interventions showed a greater improvement for the OVX-induced bone loss and the elevated serum tartrate-resistant acid phosphatase (TRAP) and alkaline phosphatase (ALP) compared with EX only. Both EX and EI interventions bettered the OVX-related reduction of BV/TV and trabecular number and thickness, and decreased the enlargement of trabecular bone separation (Tb. Sp); the improvement for BV/TV and Tb. Sp was greater in EI group. Furthermore, EX and EI treatment significantly increased the number of ALP+ cells and mineralized nodule areas compared with OVX group; the change was higher in EI group. Additionally, in comparison to OVX rats, the protein and mRNA expression of β-catenin, phosphorylated-Akt (p-Akt) or Akt, ERα, and Runt-related transcription factor 2 (Runx2) in osteoblasts were elevated in EX and EI intervention rats, with greater change observed in EI group. The upregulated β-catenin and Akt mRNA levels in EX and EI groups was depressed by ICI182780 treatment, and the difference in β-catenin and Akt mRNA levels between EX and EI groups was no longer significant. Conclusively, the combination of Icariin and exercise significantly prevent OVX-induced bone loss and increase osteoblast differentiation and the ability of mineralization compared with exercise alone; the changes might be regulated partly by ERα/Akt/β-catenin pathway.
Highlights
Osteoporosis is a common aged-related skeletal disorder characterized by compromised bone strength predisposing the older adults to high risk of fracture [1,2]
Interventions markedly alleviated bone wasting, with more bone mineral density (BMD) increment found in exercise and Icariin (EI) group
Interventions decreased serum biomarkers and elevated E2 concentrations, and the beneficial changes in E2, alkaline phosphatase (ALP), and tartrate-resistant acid phosphatase (TRAP) were greater for EI treatment compared with EX intervention only (Table 1)
Summary
Osteoporosis is a common aged-related skeletal disorder characterized by compromised bone strength predisposing the older adults to high risk of fracture [1,2]. Osteoporosis-related medical care causes a heavy burden both on society and families [3,4]. To find effective therapeutic strategies becomes one emergent clinical research task [5,6]. Compelling evidence has confirmed that exercise generates beneficial effects on loading sites in osteoporotic individuals [7,8,9]; it has been recognized as an effective way to prevent age-related bone loss and a promising strategy for fracture reduction [10,11,12,13,14]. Res. Public Health 2019, 16, 3779; doi:10.3390/ijerph16193779 www.mdpi.com/journal/ijerph
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