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Cell-free culture supernatant of Lactobacillus curvatus Wikim38 inhibits RANKL-induced osteoclast differentiation and ameliorates bone loss in ovariectomized mice
Authors:A-R Jang  J-S Park  D-K Kim  J-Y Park  J-H Ahn  D-Y Kim  T-S Lee  J-Y Chang  J-H Choi  J-H Park
Institution:1. Laboratory Animal Medicine, College of Veterinary Medicine, Chonnam National University, Gwangju, Republic of Korea;2. Laboratory Animal Center, Daegu-Gyeongbuk Medical Innovation Foundation, Daegu, Republic of Korea;3. Microbiology and Functionality Research Group, World Institute of Kimchi, Gwangju, Republic of Korea
Abstract:This study was conducted to investigate the inhibitory effects of the cell-free culture supernatant of Lactobacillus curvatus Wikim 38 (LC38-CS) on RANKL-induced osteoclast differentiation and bone loss in a mice model of ovariectomy-induced post-menopausal osteoporosis. LC38-CS inhibited the RANKL-induced differentiation of bone marrow-derived macrophages (BMDMs) into osteoclasts in a dose-dependent manner. F-actin ring formation and bone resorption were also reduced by LC38-CS treatment of RANKL-treated BMDMs. In addition, LC38-CS decreased the RANKL-induced activation of the TRAF6/NF-κB/MAPKs axis at the early stage and the expression of osteoclastogenesis-related genes in BMDMs treated with RANKL. PRMT1 and ADMA levels, new biomarkers for osteoclastogenesis, were decreased by LC38-CS treatment. The administration of LC38-CS increased bone volume and bone mineral density in ovariectomized mice in μ-CT analysis. These findings suggest that LC38-CS inhibited RANKL-induced osteoclast differentiation by the downregulation of molecular mechanisms and exerted anti-osteoporotic effects.
Keywords:Lactobacillus curvatus  osteoporosis  ovariectomized mice  postbiotics supplementation  RANKL-induced osteoclast
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