Neohesperidin suppresses osteoclast differentiation, bone resorption and ovariectomised-induced osteoporosis in mice.
Excessive bone resorption by osteoclasts plays an important role in osteoporosis. Bone loss occurs in ovariectomised (OVX) mice in a similar manner to that in humans, so this model is suitable for evaluating potential new therapies for osteoporosis. Neohesperidin (NE) is a flavonoid compound isolated from citrus fruits. Its role in bone metabolism is unknown. In this study we found that neohesperidin inhibits osteoclast differentiation, bone resorption and the expression of osteoclast marker genes, tartrate-resistant acid phosphatase and cathepsin K. In addition, neohesperidin inhibited receptor activator of NF-κB ligand (RANKL)-induced activation of NF-κB, and the degradation of inhibitor of kappa B-alpha (IκBα). Furthermore, neohesperidin inhibited RANKL induction of nuclear factor of activated T-cells (NFAT) and calcium oscillations. In vivo treatment of ovariectomised mice with neohesperidin protected against bone loss in mice. The results suggest neohesperidin has anti-osteoclastic effects in vitro and in vivo and possesses therapeutic potential as a natural anti-catabolic treatment in osteoporosis.
Department of Orthopaedic Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi 530021, China; Research Centre for Regenerative Medicine, Guangxi Medical University, Guangxi 530021, China; Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi 530021, China.
Zhen
Z
Tan
Department of Orthopaedic Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi 530021, China; Research Centre for Regenerative Medicine, Guangxi Medical University, Guangxi 530021, China; Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi 530021, China; School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, WA 6009, Australia.
Jianwen
J
Cheng
Department of Orthopaedic Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi 530021, China; Research Centre for Regenerative Medicine, Guangxi Medical University, Guangxi 530021, China; Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi 530021, China; School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, WA 6009, Australia.
Qian
Q
Liu
School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, WA 6009, Australia.
Lin
L
Zhou
School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, WA 6009, Australia.
Jacob
J
Kenny
Research Centre for Regenerative Medicine, Guangxi Medical University, Guangxi 530021, China; Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi 530021, China.
Tao
T
Wang
Research Centre for Regenerative Medicine, Guangxi Medical University, Guangxi 530021, China; Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi 530021, China.
Xixi
X
Lin
School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, WA 6009, Australia.
Jinbo
J
Yuan
The Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
Julian M W
JMW
Quinn
School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, WA 6009, Australia.
Jennifer
J
Tickner
School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, WA 6009, Australia; The National Key Discipline and the Orthopedic Laboratory, Guangzhou University of Chinese Medicine, Guangzhou, Guangdong 510006, China.
Guoju
G
Hong
Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedics, Shanghai Jiao Tong University School of Medicine, Ninth People's Hospital, Shanghai 200011, China.
An
A
Qin
Department of Orthopaedic Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi 530021, China; Research Centre for Regenerative Medicine, Guangxi Medical University, Guangxi 530021, China; Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi 530021, China. Electronic address: zhaojinmin@126.com.
Jinmin
J
Zhao
Department of Orthopaedic Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi 530021, China; Research Centre for Regenerative Medicine, Guangxi Medical University, Guangxi 530021, China; School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, WA 6009, Australia. Electronic address: jiake.xu@uwa.edu.au.
Jiake
J
Xu
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D001854:Bone Marrow Cells / Q000166:cytology; D001862:Bone Resorption / Q000150:complications / Q000378:metabolism / Q000473:pathology*; D002118:Calcium / Q000378:metabolism; D056657:Cathepsin K / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects*; D002478:Cells, Cultured; D005260:Female; D017930:Genes, Reporter; D006569:Hesperidin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology; D008156:Luciferases / Q000378:metabolism; D008264:Macrophages / Q000187:drug effects / Q000378:metabolism; D008810:Mice, Inbred C57BL; D000072000:NF-KappaB Inhibitor alpha / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D050778:NFATC Transcription Factors / Q000378:metabolism; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism / Q000473:pathology*; D010024:Osteoporosis / Q000150:complications / Q000209:etiology* / Q000378:metabolism / Q000473:pathology*; D010052:Ovariectomy / Q000009:adverse effects*; D059748:Proteolysis / Q000187:drug effects; D053245:RANK Ligand / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D000071681:Tartrate-Resistant Acid Phosphatase / Q000235:genetics / Q000378:metabolism
D016328:NF-kappa B; D050778:NFATC Transcription Factors; D053245:RANK Ligand; D012333:RNA, Messenger; D000072000:NF-KappaB Inhibitor alpha; D006569:Hesperidin; D008156:Luciferases; D000071681:Tartrate-Resistant Acid Phosphatase; D056657:Cathepsin K; C546526:neohesperidin; D002118:Calcium
Inhibition; Neohesperidin; Osteoclasts; Osteoporosis