Icariin attenuates titanium-particle inhibition of bone formation by activating the Wnt/β-catenin signaling pathway in vivo and in vitro

• Published in: Scientific reports 2016-03, Vol.6 (1), p.23827-23827, Article 23827
• Main Authors: Wang, Junhua, Tao, Yunxia, Ping, Zichuan, Zhang, Wen, Hu, Xuanyang, Wang, Yijun, Wang, Liangliang, Shi, Jiawei, Wu, Xiexing, Yang, Huilin, Xu, Yaozeng, Geng, Dechun
• Format: Article
• Language: English
• Subjects: 631/154/152; 631/61/54/152; 82/51; Administration, Topical; Animals; beta Catenin - agonists; beta Catenin - antagonists & inhibitors; beta Catenin - genetics; beta Catenin - metabolism; Bone-Implant Interface - pathology; Bridged Bicyclo Compounds, Heterocyclic - pharmacology; Cell Differentiation; Drugs, Chinese Herbal - pharmacology; Female; Flavonoids - antagonists & inhibitors; Flavonoids - pharmacology; Gene Expression; Humanities and Social Sciences; Mesenchymal Stromal Cells - cytology; Mesenchymal Stromal Cells - drug effects; Mesenchymal Stromal Cells - metabolism; Mice; Mice, Inbred C57BL; multidisciplinary; Osteoblasts - cytology; Osteoblasts - drug effects; Osteoblasts - metabolism; Osteoclasts - cytology; Osteoclasts - drug effects; Osteoclasts - metabolism; Osteogenesis - drug effects; Osteolysis - chemically induced; Osteolysis - metabolism; Osteolysis - pathology; Osteolysis - prevention & control; Primary Cell Culture; Pyrimidinones - pharmacology; Science; Science (multidisciplinary); Signal Transduction - drug effects; Skull - drug effects; Skull - metabolism; Skull - surgery; Titanium - adverse effects
• ISSN: 2045-2322; 2045-2322
• DOI: 10.1038/srep23827

Wear-debris-induced periprosthetic osteolysis (PIO) is a common clinical condition following total joint arthroplasty, which can cause implant instability and failure. The host response to wear debris promotes bone resorption and impairs bone formation. We previously demonstrated that icariin suppressed wear-debris-induced osteoclastogenesis and attenuated particle-induced osteolysis in vivo . Whether icariin promotes bone formation in a wear-debris-induced osteolytic site remains unclear. Here, we demonstrated that icariin significantly attenuated titanium-particle inhibition of osteogenic differentiation of mesenchymal stem cells (MSCs). Additionally, icariin increased bone mass and decreased bone loss in titanium-particle-induced osteolytic sites. Mechanistically, icariin inhibited decreased β-catenin stability induced by titanium particles in vivo and in vitro . To confirm icariin mediated its bone-protective effects via the Wnt/β-catenin signaling pathway, we demonstrated that ICG-001, a selective Wnt/β-catenin inhibitor, attenuated the effects of icariin on MSC mineralization in vitro and bone formation in vivo . Therefore, icariin could induce osteogenic differentiation of MSCs and promote new bone formation at a titanium-particle-induced osteolytic site via activation of the Wnt/β-catenin signaling pathway. These results further support the protective effects of icariin on particle-induced bone loss and provide novel mechanistic insights into the recognized bone-anabolic effects of icariin and an evidence-based rationale for its use in PIO treatment.