title: Strontium ranelate inhibits titanium-particle-induced osteolysis by restraining inflammatory osteoclastogenesis in vivo.
abstract: Wear-particle-induced osteolysis is considered to be the main reason for revision after arthroplasty. Although the exact mechanism remains unclear, inflammatory osteoclastogenesis plays an important role in this process. Strontium ranelate (SR) was found to have a therapeutic effect on osteoporosis in postmenopausal women. Based on prior studies, the present authors hypothesized that SR prevents wear-particle-induced osteolysis through restraining inflammatory osteoclastogenesis. The present study used 80 male C57BL/J6 mice to test this hypothesis in a murine osteolysis model. All experimental animals were randomly divided into four groups: a control group; a SR group; a titanium group; and a titanium+SR group. Once titanium particles had been implanted in mice, the mice were administered SR (900 mg kg(-1) day(-1)) by gavage for 14 days. After 14 days, the calvaria were collected for micro-computed tomography (μCT), histological and molecular analysis. The results of μCT and histomorphometric analysis demonstrated that SR markedly inhibited bone resorption and the generation of tartrate-resistant acid-phosphatase-positive cells in vivo, compared with titanium-stimulated calvaria. Reverse transcription polymerase chain reaction and ELISAs showed that SR stimulated the mRNA and protein expression of osteoprotegerin, and inhibited gene and protein expression of receptor activators of nuclear factor-kappa B ligand in titanium-particle-charged calvaria. In addition, SR obviously reduced the secretion of tumor necrosis factor-α and interleukin-1β in the calvaria of the titanium group. It was concluded that SR inhibits titanium-induced osteolysis by restraining inflammatory osteoclastogenesis, and that it could be developed as a new drug to prevent and treat aseptic loosening.
authors: State Key Laboratory of Genetic Engineering, Fudan University, 220 Handan Road, Shanghai 200433, China.
authors: Xing
authors: X
authors: Liu
authors: Department of Orthopedics, The First Affiliated Hospital of Soochow University, 188, shi zi Road, Suzhou 215006, China.
authors: Shijun
authors: S
authors: Zhu
authors: Department of Orthopedics, The First Affiliated Hospital of Soochow University, 188, shi zi Road, Suzhou 215006, China.
authors: Jingfu
authors: J
authors: Cui
authors: Department of Orthopedics, The First Affiliated Hospital of Soochow University, 188, shi zi Road, Suzhou 215006, China.
authors: Hongguo
authors: H
authors: Shao
authors: Orthopedic Institute, Soochow University, Suzhou 215006, China.
authors: Wen
authors: W
authors: Zhang
authors: Department of Orthopedics, The First Affiliated Hospital of Soochow University, 188, shi zi Road, Suzhou 215006, China.
authors: Huilin
authors: H
authors: Yang
authors: Department of Orthopedics, The First Affiliated Hospital of Soochow University, 188, shi zi Road, Suzhou 215006, China.
authors: Yaozeng
authors: Y
authors: Xu
authors: Department of Orthopedics, The First Affiliated Hospital of Soochow University, 188, shi zi Road, Suzhou 215006, China. Electronic address: szgengdc@163.com.
authors: Dechun
authors: D
authors: Geng
authors: State Key Laboratory of Genetic Engineering, Fudan University, 220 Handan Road, Shanghai 200433, China. Electronic address: yulong201@aliyun.com.
authors: Long
authors: L
authors: Yu
mesh_terms: D000135:Acid Phosphatase / Q000378:metabolism; D000818:Animals; D007249:Inflammation / Q000473:pathology*; D053583:Interleukin-1beta / Q000235:genetics / Q000378:metabolism; D007527:Isoenzymes / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010012:Osteogenesis / Q000187:drug effects*; D010014:Osteolysis / Q000139:chemically induced* / Q000188:drug therapy*; D053244:Osteoprotegerin / Q000235:genetics / Q000378:metabolism; D053245:RANK Ligand / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012886:Skull / Q000000981:diagnostic imaging / Q000473:pathology; D013194:Staining and Labeling; D000071681:Tartrate-Resistant Acid Phosphatase; D013876:Thiophenes / Q000494:pharmacology / Q000627:therapeutic use*; D014025:Titanium / Q000009:adverse effects*; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism; D055114:X-Ray Microtomography
chemical_list: D053583:Interleukin-1beta; D007527:Isoenzymes; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; D013876:Thiophenes; D014409:Tumor Necrosis Factor-alpha; C081587:strontium ranelate; D014025:Titanium; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase
keywords: Aseptic loosening; RANKL; Strontium ranelate; TNF-α; Wear particle