Neohesperidin suppresses osteoclast differentiation, bone resorption and ovariectomised-induced osteoporosis in mice

Zhen Tan; Jianwen Cheng; Qian Liu; Lin Zhou; Jacob Kenny; Tao Wang; Xixi Lin; Jinbo Yuan; Julian M W Quinn; Jennifer Tickner; Guoju Hong; An Qin; Jinmin Zhao; Jiake Xu

doi:10.1016/j.mce.2016.09.026

Neohesperidin suppresses osteoclast differentiation, bone resorption and ovariectomised-induced osteoporosis in mice

Mol Cell Endocrinol. 2017 Jan 5:439:369-378. doi: 10.1016/j.mce.2016.09.026. Epub 2016 Sep 21.

Authors

Zhen Tan¹, Jianwen Cheng², Qian Liu², Lin Zhou³, Jacob Kenny³, Tao Wang⁴, Xixi Lin⁴, Jinbo Yuan³, Julian M W Quinn⁵, Jennifer Tickner³, Guoju Hong⁶, An Qin⁷, Jinmin Zhao⁸, Jiake Xu⁹

Affiliations

¹ 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.
² 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.
³ School of Pathology and Laboratory Medicine, The University of Western Australia, Perth, WA 6009, Australia.
⁴ Research Centre for Regenerative Medicine, Guangxi Medical University, Guangxi 530021, China; Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi 530021, China.
⁵ The Garvan Institute of Medical Research, Darlinghurst, NSW, Australia.
⁶ 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.
⁷ Shanghai Key Laboratory of Orthopaedic Implant, Department of Orthopaedics, Shanghai Jiao Tong University School of Medicine, Ninth People's Hospital, Shanghai 200011, China.
⁸ 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.
⁹ 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.

PMID: 27664516
DOI: 10.1016/j.mce.2016.09.026

Abstract

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.

Keywords: Inhibition; Neohesperidin; Osteoclasts; Osteoporosis.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / drug effects
Blotting, Western
Bone Marrow Cells / cytology
Bone Resorption / complications
Bone Resorption / metabolism
Bone Resorption / pathology*
Calcium / metabolism
Cathepsin K / metabolism
Cell Differentiation / drug effects*
Cells, Cultured
Female
Genes, Reporter
Hesperidin / analogs & derivatives*
Hesperidin / chemistry
Hesperidin / pharmacology
Luciferases / metabolism
Macrophages / drug effects
Macrophages / metabolism
Mice, Inbred C57BL
NF-KappaB Inhibitor alpha / metabolism
NF-kappa B / metabolism
NFATC Transcription Factors / metabolism
Osteoclasts / drug effects
Osteoclasts / metabolism
Osteoclasts / pathology*
Osteoporosis / complications
Osteoporosis / etiology*
Osteoporosis / metabolism
Osteoporosis / pathology*
Ovariectomy / adverse effects*
Proteolysis / drug effects
RANK Ligand / pharmacology
RNA, Messenger / genetics
RNA, Messenger / metabolism
Real-Time Polymerase Chain Reaction
Tartrate-Resistant Acid Phosphatase / genetics
Tartrate-Resistant Acid Phosphatase / metabolism

Substances

NF-kappa B
NFATC Transcription Factors
RANK Ligand
RNA, Messenger
NF-KappaB Inhibitor alpha
Hesperidin
Luciferases
Tartrate-Resistant Acid Phosphatase
Cathepsin K
neohesperidin
Calcium