title: Lupeol acetate ameliorates collagen-induced arthritis and osteoclastogenesis of mice through improvement of microenvironment.
abstract: Lupeol has been shown with anti-inflammation and antitumor capability, however, the poor bioavailability limiting its applications in living subjects. Lupeol acetate (LA), a derivative of lupeol, shows similar biological activities as lupeol but with better bioavailability. Here RAW 264.7 cells and bone marrow-derived macrophages (BMDMs) stimulated by lipopolysaccharide (LPS) were treated with 0-80μM of LA, and assayed for TNF-α, IL-1β, COX-2, MCP-1 using Western blotting. Moreover, osteoclatogenesis was examined with reverse transcription PCR (RT-PCR) and tartrate-resistant acid phosphatase (TRAP) staining. For in vivo study, collagen-induced arthritis (CIA)-bearing DBA/1J mice were randomly separated into three groups: vehicle, LA-treated (50mg/kg) and curcumin-treated (100mg/kg). Therapeutic efficacies were assayed by the clinical score, expression levels of serum cytokines including TNF-α and IL-1β, (18)F-fluorodeoxyglucose ((18)F-FDG) microPET/CT and histopathology. The results showed that LA could inhibit the activation, migration, and formation of osteoclastogenesis of macrophages in a dose-dependent manner. In RA-bearing mice, the expressions of inflammation-related cytokines were suppressed, and clinical symptoms and bone erosion were ameliorated by LA. The accumulation of (18)F-FDG in the joints of RA-bearing mice was also significantly decreased by LA. The results indicate that LA significantly improves the symptoms of RA by down-regulating expressions of inflammatory cytokines and osteoclastogenesis.
authors.affiliation: Dept of Orthopedic Surgery, Changhua Christian Hospital, Changhua, Taiwan.
authors.forename: Wei-Hsun
authors.initials: WH
authors.lastname: Wang
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan.
authors.forename: Hui-Yen
authors.initials: HY
authors.lastname: Chuang
authors.affiliation: Department of Radiation Oncology, Chang-Gung Memorial Hospital, Taoyen, Taiwan.
authors.forename: Chien-Hui
authors.initials: CH
authors.lastname: Chen
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan; Department of Radiation Oncology, Hsinchu Branch, Mackay Memorial Hospital, Hsinchu, Taiwan.
authors.forename: Wun-Ke
authors.initials: WK
authors.lastname: Chen
authors.affiliation: Department of Biomedical Imaging and Radiological Sciences, National Yang-Ming University, Taipei, Taiwan; Biophotonics & Molecular Imaging Research Center (BMIRC), National Yang-Ming University, Taipei, Taiwan. Electronic address: jjhwang@ym.edu.tw.
authors.forename: Jeng-Jong
authors.initials: JJ
authors.lastname: Hwang
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000188:drug therapy* / Q000473:pathology*; D001854:Bone Marrow Cells; D002454:Cell Differentiation / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D060833:Cellular Microenvironment / Q000187:drug effects; D018932:Chemokine CCL2 / Q000378:metabolism; D051546:Cyclooxygenase 2 / Q000378:metabolism; D004195:Disease Models, Animal; D053583:Interleukin-1beta / Q000378:metabolism; D008070:Lipopolysaccharides; D008264:Macrophages / Q000378:metabolism; D051379:Mice; D010010:Osteoclasts / Q000187:drug effects / Q000473:pathology*; D010012:Osteogenesis / Q000187:drug effects; D053978:Pentacyclic Triterpenes / Q000494:pharmacology / Q000627:therapeutic use*; D053245:RANK Ligand / Q000494:pharmacology; D000067996:RAW 264.7 Cells; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D000094042:Lupanes
chemical_list: D018932:Chemokine CCL2; D051546:Cyclooxygenase 2; D053583:Interleukin-1beta; D008070:Lipopolysaccharides; D053978:Pentacyclic Triterpenes; D053245:RANK Ligand; D014409:Tumor Necrosis Factor-alpha; C491768:Ccl2 protein, mouse; C010480:lupeol; D000094042:Lupanes
keywords: Collagen-induced arthritis; Lupeol acetate; Macrophage; Osteoclastogenesis; RANKL