Stimulation of Wnt/β-catenin signaling pathway is involved in the effect of naringin on the prevention of disuse osteoporosis

Objective To investigate whether naringin has a role in the prevention of disuse osteoporosis and the mechanisms that may be involved. Methods Disuse osteoporosis in male SD rats was induced by tail suspension, which were then randomly divided into four groups as following: the Hindlimb Suspension group(HLS), 30 mg·kg-1·d-1, 100 mg·kg-1·d-1 and 300 mg· kg-1·d-1 Naringin-treating group. Rats in the control group and suspension only group received equivalent saline as vehicle. Another equal amount of rats was selected as the Control group. Four weeks following the operation, all rats were sacrificed. Dual energy X-ray absorptionmetry(DXA)was used to analyze the distal femoral BMD, Micro-CT was used to test the trabecular microstructure in distal femur, biomechanical tests were used to analyze femoral mechanical properties and bone turnover markers in serum were tested by ELISA. The expressions of periostin, sclerostin and nucleus β-catenin in tibias were evaluated by qRT-PCR and Western-blot. The femurs were immunohistochemical stained for periostin and sclerostin. Results Four weeks after operation, BMD of distal femurs in HLS group decreased significantly compared with the control group, together with the dramatical deterioration of distal femoral trabecular microstructure and femur mechanical properties. The serum level of CTX-1 increased significantly while that of P1NP decreased. PCR and Western-blot indicated that the expression of periostin and nucleus β-catenin in tibias decreased dramatically, while sclerostin increased. The periostin secreted by periosteal osteoblasts decreased significantly while the intensity of positive immunostaining with sclerostin in osteocytes increased. Naringin at 100 mg·kg-1·d-1 and 300 mg·kg-1·d-1 significantly inhibited hindlimb suspension-induced decreasing of BMD in distal femur, together with the deterioration of trabecular microstructure and femur mechanical properties, increased serum P1NP level and decreased CTX-1. Naringin increased the expression of periostin and nucleus β-catenin and decreased the level of sclerositn. Conclusion Naringin could prevent the progress of disuse osteoporosis in rats, which may be mediated by the increased expression of periostin and subsequently inhibition of sclerostin and activation of Wnt/β-catenin signaling pathways. Key words: Osteoporosis; Drynaria fortunei; beta Catenin; Wnt signaling pathway