title: Icariin attenuates titanium-particle inhibition of bone formation by activating the Wnt/β-catenin signaling pathway in vivo and in vitro.
abstract: 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.
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, 188, shi zi Road, Suzhou, 215006, China.
authors.forename: Junhua
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, 188, shi zi Road, Suzhou, 215006, China.
authors.forename: Yunxia
authors.initials: Y
authors.lastname: Tao
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, 188, shi zi Road, Suzhou, 215006, China.
authors.forename: Zichuan
authors.initials: Z
authors.lastname: Ping
authors.affiliation: Orthopedic Institute, Soochow University, 708, ren min Road, Suzhou, 215006, China.
authors.forename: Wen
authors.initials: W
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, 188, shi zi Road, Suzhou, 215006, China.
authors.forename: Xuanyang
authors.initials: X
authors.lastname: Hu
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, 188, shi zi Road, Suzhou, 215006, China.
authors.forename: Yijun
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, 188, shi zi Road, Suzhou, 215006, China.
authors.forename: Liangliang
authors.initials: L
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, 188, shi zi Road, Suzhou, 215006, China.
authors.forename: Jiawei
authors.initials: J
authors.lastname: Shi
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, 188, shi zi Road, Suzhou, 215006, China.
authors.forename: Xiexing
authors.initials: X
authors.lastname: Wu
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, 188, shi zi Road, Suzhou, 215006, China.
authors.forename: Huilin
authors.initials: H
authors.lastname: Yang
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, 188, shi zi Road, Suzhou, 215006, China.
authors.forename: Yaozeng
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Orthopedics, The First Affiliated Hospital of Soochow University, 188, shi zi Road, Suzhou, 215006, China.
authors.forename: Dechun
authors.initials: D
authors.lastname: Geng
mesh_terms: D000287:Administration, Topical; D000818:Animals; D000069343:Bone-Implant Interface / Q000473:pathology; D019086:Bridged Bicyclo Compounds, Heterocyclic / Q000494:pharmacology; D002454:Cell Differentiation; D004365:Drugs, Chinese Herbal / Q000494:pharmacology*; D005260:Female; D005419:Flavonoids / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D015870:Gene Expression; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects*; D010014:Osteolysis / Q000139:chemically induced / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D061251:Primary Cell Culture; D011744:Pyrimidinones / Q000494:pharmacology; D015398:Signal Transduction / Q000187:drug effects*; D012886:Skull / Q000187:drug effects / Q000378:metabolism / Q000601:surgery; D014025:Titanium / Q000009:adverse effects*; D051176:beta Catenin / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism
chemical_list: D019086:Bridged Bicyclo Compounds, Heterocyclic; C495267:CTNNB1 protein, mouse; D004365:Drugs, Chinese Herbal; D005419:Flavonoids; C492448:ICG 001; D011744:Pyrimidinones; D051176:beta Catenin; D014025:Titanium; C056599:icariin