title: Icariin Augments Bone Formation and Reverses the Phenotypes of Osteoprotegerin-Deficient Mice through the Activation of Wnt/ β -Catenin-BMP Signaling.
abstract: Icariin has been mostly reported to enhance bone fracture healing and treat postmenopausal osteoporosis in ovariectomized animal model. As another novel animal model of osteoporosis, there is few publication about the effect of Icariin on osteoprotegerin-deficient mice. Therefore, the goal of this study is to find the effect on bone formation and underlying mechanisms of Icariin in osteoprotegerin (OPG) knockout (KO) mice. We found that Icariin significantly stimulated new bone formation after local injection over the surface of calvaria at the dose of 5 mg/kg per day. With this dose, Icariin was also capable of significantly reversing OPG-deficient-induced bone loss and bone strength reduction. Real-time PCR analysis showed that Icariin significantly upregulated the expression of BMP2, BMP4, RUNX2, OC, Wnt1, and Wnt3a in OPG KO mice. Icariin also significantly increased the expression of AXIN2, DKK1, TCF1, and LEF1, which are the direct target genes of β -catenin signaling. The in vitro studies showed that Icariin induced osteoblast differentiation through the activation of Wnt/ β -catenin-BMP signaling by in vitro deletion of the β -catenin gene using β -catenin(fx/fx) mice. Together, our findings demonstrate that Icariin significantly reverses the phenotypes of OPG-deficient mice through the activation of Wnt/ β -catenin-BMP signaling.
authors.affiliation: Spine Research Institute, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China ; Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
authors.forename: Xiao-Feng
authors.initials: XF
authors.lastname: Li
authors.affiliation: Spine Research Institute, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China ; Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Xu
authors.affiliation: Spine Research Institute, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China ; Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
authors.forename: Yong-Jian
authors.initials: YJ
authors.lastname: Zhao
authors.affiliation: Spine Research Institute, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China ; Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
authors.forename: De-Zhi
authors.initials: DZ
authors.lastname: Tang
authors.affiliation: Shanghai Changzheng Hospital, Shanghai 200003, China.
authors.forename: Guo-Hua
authors.initials: GH
authors.lastname: Xu
authors.affiliation: Biology Department, St. John Fisher College, Rochester, NY 14618, USA.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Holz
authors.affiliation: Spine Research Institute, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China ; Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.affiliation: Spine Research Institute, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China ; Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
authors.forename: Shao-Dan
authors.initials: SD
authors.lastname: Cheng
authors.affiliation: Spine Research Institute, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China ; Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Shi
authors.affiliation: Spine Research Institute, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China ; Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China.
authors.forename: Yong-Jun
authors.initials: YJ
authors.lastname: Wang