title: β-Carotene suppresses osteoclastogenesis and bone resorption by suppressing NF-κB signaling pathway.
abstract: OBJECTIVE
  β-Carotene is a natural anti-oxidant, which has been used for treatment of cancer and cardiovascular diseases. Recently, the ameliorating function of β-carotene in osteoporosis has been implicated. However, the precise mechanism of β-carotene in prevention and treatment of osteoporosis is largely unknown. In the present study, we aimed to elucidate how β-carotene affects osteoclast formation and bone resorption.
  
  
  METHODS
  Bone marrow-derived monocytes/-macrophages (BMM) were exposed to 0.05, 0.1, 0.2, 0.4 and 0.6μM β-carotene, followed by evaluation of cell viability, lactate dehydrogenase (LDH) release, receptor activator of nuclear factor kappa B ligand (RANKL)-induced osteoclastogenesis and resorption pits formation. Key factors in nuclear factor kappa B (NF-ĸB) and mitogen-activated protein kinases (MAPK) pathways were evaluated with western blot after BMM cells were exposed to RANKL and β-carotene. The effects of β-carotene in nuclear factor of activated T-cells cytoplasmic 1 (NFATc1), c-Fos and cathepsin K (CTSK) expression were also evaluated.
  
  
  RESULTS
  β-Carotene significantly inhibited BMM viability and promoted LDH release at concentrations of 0.4 and 0.6μM. A decrease in RANKL-induced osteoclastogenesis and resorption was also observed after β-carotene treatment. β-Carotene attenuated the NF-ĸB pathway activation by RANKL, with no effect on MAPK pathway. β-Carotene suppressed the upregulation of NFATc1 and c-Fos by RANKL.
  
  
  CONCLUSIONS
  We clarified the anti-osteoclastogenic role of β-carotene, which is mediated by NF-κB signaling.
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Sixth People's Hospital East Affiliated to Shanghai University of Medicine & Health Sciences, Shanghai 201306, China; Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Wang
authors.affiliation: Department of Emergency, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China.
authors.forename: Nan
authors.initials: N
authors.lastname: Wang
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Youshui
authors.initials: Y
authors.lastname: Gao
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Zubin
authors.initials: Z
authors.lastname: Zhou
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Liu
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Chenhao
authors.initials: C
authors.lastname: Pan
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China.
authors.forename: Peipei
authors.initials: P
authors.lastname: Yin
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. Electronic address: yuxw@sjtu.edu.cn.
authors.forename: Xiaowei
authors.initials: X
authors.lastname: Yu
authors.affiliation: Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. Electronic address: 13311828153@189.cn.
authors.forename: Mingjie
authors.initials: M
authors.lastname: Tang
mesh_terms: D000818:Animals; D015153:Blotting, Western; D001862:Bone Resorption / Q000517:prevention & control*; D002454:Cell Differentiation; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D008264:Macrophages / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D016328:NF-kappa B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects* / Q000502:physiology; D000072664:Provitamins / Q000494:pharmacology; D015398:Signal Transduction; D019207:beta Carotene / Q000494:pharmacology*
chemical_list: D016328:NF-kappa B; D000072664:Provitamins; D019207:beta Carotene
keywords: Anti-oxidant; Bone resorption; NF-κB; Osteoclastogenesis; β-Carotene