Feng Wang1, Nan Wang2, Youshui Gao3, Zubin Zhou3, Wei Liu3, Chenhao Pan3, Peipei Yin3, Xiaowei Yu4, Mingjie Tang5. 1. 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. 2. Department of Emergency, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, Henan 450052, China. 3. Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. 4. Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. Electronic address: yuxw@sjtu.edu.cn. 5. Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People's Hospital, Shanghai 200233, China. Electronic address: 13311828153@189.cn.
Abstract
AIMS: 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. MAIN 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. KEY FINDINGS: 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. SIGNIFICANCE: We clarified the anti-osteoclastogenic role of β-carotene, which is mediated by NF-κB signaling.
AIMS: 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. MAIN 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. KEY FINDINGS: 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. SIGNIFICANCE: We clarified the anti-osteoclastogenic role of β-carotene, which is mediated by NF-κB signaling.