title: Scutellarin inhibits RANKL-mediated osteoclastogenesis and titanium particle-induced osteolysis via suppression of NF-κB and MAPK signaling pathway.
abstract: Aseptic prosthetic loosening is a major complication after hip joint replacement. Wear particle-induced periprosthetic osteolysis plays a key role in aseptic prosthetic loosening. Attempting to modulate receptor activator of nuclear factor-κB (RANKL) mediated signaling pathways is a promising strategy to prevent aseptic prosthetic loosening. In the present study, we determined the effect of scutellarin (SCU) on titanium (Ti) particle-induced osteolysis in a mouse calvarial model and RANKL-mediated osteoclastogenesis. We determined that SCU, the major effective constituent of breviscapine isolated from a Chinese herb, has potential effects on preventing Ti particle-caused osteolysis in calvarial model of mouse. In vitro, SCU could suppress RANKL-mediated osteoclastogenesis, the function of osteoclast bone resorption, and the expression levels of osteoclast-specific genes (tartrate-resistant acid phosphatase (TRAP), cathepsin K, c-Fos, NFATc1). Further investigation indicated that SCU could inhibit RANKL-mediated MAPK and NF-κB signaling pathway, including JNK1/2, p38, ERK1/2, and IκBα phosphorylation. Taken together, these results indicate that SCU could inhibit osteoclastogenesis and prevent Ti particle-induced osteolysis by suppressing RANKL-mediated MAPK and NF-κB signaling pathway. These results suggest that SCU is a promising therapeutic agent for preventing wear particle-induced periprosthetic osteolysis.
authors.affiliation: Department of Orthopedics, Xiangya Second Hospital, Central South University, Changsha, Hunan 410012, China. Electronic address: zhaoshuai19870624@163.com.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Orthopedics, Clinical medical college of Yangzhou University, Nantong West Road 98, Yangzhou, Jiangsu 225001, China; Orthopedics Institute, Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu 225001, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.affiliation: Department of Orthopedics, Xiangya Second Hospital, Central South University, Changsha, Hunan 410012, China; Department of Orthopedics, Clinical medical college of Yangzhou University, Nantong West Road 98, Yangzhou, Jiangsu 225001, China; Orthopedics Institute, Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu 225001, China.
authors.forename: Xiaolei
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Orthopedics, Xiangya Second Hospital, Central South University, Changsha, Hunan 410012, China; Department of Orthopedics, Clinical medical college of Yangzhou University, Nantong West Road 98, Yangzhou, Jiangsu 225001, China; Orthopedics Institute, Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu 225001, China. Electronic address: jingchengwyz@163.com.
authors.forename: Jingcheng
authors.initials: J
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Xiangya Second Hospital, Central South University, Changsha, Hunan 410012, China; Department of Orthopedics, Clinical medical college of Yangzhou University, Nantong West Road 98, Yangzhou, Jiangsu 225001, China; Orthopedics Institute, Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu 225001, China. Electronic address: yanlianqi@126.com.
authors.forename: Lianqi
authors.initials: L
authors.lastname: Yan
authors.affiliation: Department of Orthopedics, Clinical medical college of Yangzhou University, Nantong West Road 98, Yangzhou, Jiangsu 225001, China; Orthopedics Institute, Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu 225001, China.
authors.forename: Zhen
authors.initials: Z
authors.lastname: Zhang
authors.affiliation: Department of Orthopedics, Xiangya Second Hospital, Central South University, Changsha, Hunan 410012, China; Department of Orthopedics, Clinical medical college of Yangzhou University, Nantong West Road 98, Yangzhou, Jiangsu 225001, China.
authors.forename: Daxin
authors.initials: D
authors.lastname: Wang
authors.affiliation: Department of Orthopedics, Clinical medical college of Yangzhou University, Nantong West Road 98, Yangzhou, Jiangsu 225001, China; Orthopedics Institute, Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu 225001, China.
authors.forename: Jihang
authors.initials: J
authors.lastname: Dai
authors.affiliation: Department of Orthopedics, Clinical medical college of Yangzhou University, Nantong West Road 98, Yangzhou, Jiangsu 225001, China; Orthopedics Institute, Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu 225001, China.
authors.forename: Jun
authors.initials: J
authors.lastname: He
authors.affiliation: Department of Orthopedics, Clinical medical college of Yangzhou University, Nantong West Road 98, Yangzhou, Jiangsu 225001, China; Orthopedics Institute, Subei People's Hospital of Jiangsu Province, Yangzhou, Jiangsu 225001, China.
authors.forename: Shuguang
authors.initials: S
authors.lastname: Wang
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D047310:Apigenin / Q000494:pharmacology*; D001862:Bone Resorption / Q000139:chemically induced / Q000188:drug therapy*; D004365:Drugs, Chinese Herbal / Q000627:therapeutic use*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005965:Glucuronates / Q000494:pharmacology*; D006801:Humans; D008264:Macrophages / Q000187:drug effects* / Q000502:physiology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008863:Microspheres; D016328:NF-kappa B / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects* / Q000502:physiology; D010014:Osteolysis / Q000139:chemically induced / Q000188:drug therapy*; D011475:Prosthesis Failure / Q000187:drug effects*; D053245:RANK Ligand / Q000378:metabolism; D000067996:RAW 264.7 Cells; D015398:Signal Transduction / Q000187:drug effects; D014025:Titanium
chemical_list: D000893:Anti-Inflammatory Agents; D004365:Drugs, Chinese Herbal; D005965:Glucuronates; D016328:NF-kappa B; D053245:RANK Ligand; C505689:Tnfsf11 protein, mouse; C484876:scutellarin; D047310:Apigenin; D014025:Titanium; D048049:Extracellular Signal-Regulated MAP Kinases
keywords: Aseptic loosening; MAPKs; NF-κB; Osteoclast; Osteolysis; Scutellarin