title: Inhibitory effects of ursolic acid on osteoclastogenesis and titanium particle-induced osteolysis are mediated primarily via suppression of NF-κB signaling.
abstract: Ursolic acid (UA), a pentacyclic triterpenoid found in a variety of plants, has attracted considerable attention because of its important biological and pharmacological activities. However, its effect on osteoclasts and mechanism of action require further investigation. In this study, we evaluated the effects of UA on osteoclastogenesis and osteoclast-mediated osteolysis in vitro and in vivo, and explored its possible mechanism of action. The results indicated that UA could inhibit receptor activator of nuclear factor-κB ligand (RANKL)-mediated osteoclastogenesis and the bone resorptive function of osteoclasts in a concentration-dependent manner in vitro. Further, UA effectively inhibited the mRNA and protein expression of NFATc1, primarily via the suppression of nuclear factor-κB (NF-κB) signaling, and partly through the suppression of c-Jun N-terminal kinase (JNK) signaling. Additionally, UA treatment downregulated the expression of NFATc1-regulated osteoclast marker genes. Likewise, UA induced dose-dependent attenuation of titanium (Ti) particle-induced mouse calvarial bone loss, and decreased the number of tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts. In conclusion, these results demonstrate that UA protects against wear particle-induced osteolysis by suppressing osteoclast formation and function. These effects are associated with the inhibition of the NF-κB- and JNK-related signaling pathways.
authors: Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Chuan
authors: C
authors: Jiang
authors: Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Fei
authors: F
authors: Xiao
authors: School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
authors: Xinfeng
authors: X
authors: Gu
authors: Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Zanjing
authors: Z
authors: Zhai
authors: Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Xuqiang
authors: X
authors: Liu
authors: Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Wengang
authors: W
authors: Wang
authors: Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Tingting
authors: T
authors: Tang
authors: Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: You
authors: Y
authors: Wang
authors: Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Zhenan
authors: Z
authors: Zhu
authors: Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors: Kerong
authors: K
authors: Dai
authors: Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: dr_qinan@163.com.
authors: An
authors: A
authors: Qin
authors: Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital Affiliated Shanghai Jiao Tong University School of Medicine, Shanghai, China. Electronic address: jinwu_wang@163.com.
authors: Jinwu
authors: J
authors: Wang
mesh_terms: D000818:Animals; D048670:MAP Kinase Kinase 4 / Q000378:metabolism; D008297:Male; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism*; D050778:NFATC Transcription Factors / Q000378:metabolism; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology; D010014:Osteolysis / Q000139:chemically induced / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D053245:RANK Ligand / Q000096:biosynthesis; D015398:Signal Transduction / Q000187:drug effects*; D014025:Titanium / Q000009:adverse effects* / Q000494:pharmacology; D014315:Triterpenes / Q000494:pharmacology*; D000097245:Ursolic Acid
chemical_list: D048670:MAP Kinase Kinase 4; D016328:NF-kappa B; D050778:NFATC Transcription Factors; D053245:RANK Ligand; D014025:Titanium; D014315:Triterpenes; D000097245:Ursolic Acid; C494005:Nfatc1 protein, mouse; C505689:Tnfsf11 protein, mouse
keywords: NF-κB; Osteoclastogenesis; Osteolysis; Titanium particle; Ursolic acid