Nitidine chloride prevents OVX-induced bone loss via suppressing NFATc1-mediated osteoclast differentiation.
Nitidine chloride (NC), a bioactive alkaloid isolated from Zanthoxylum nitidum, has been used as a herbal ingredient in toothpaste that prevents cavities for decades. It also displays potential antitumor and anti-inflammation properties. However, its anticatabolic effect on bone is not known. We investigated the effect of NC on osteoclastogenesis, bone resorption and RANKL-induced NF-κB and NFATc1 signalling. In mouse-derived bone marrow monocytes (BMMs), NC suppressed RANKL-induced multinucleated tartrate-resistant acid phosphatase (TRAP)-positive osteoclast formation and bone resorption in a dose dependent manner. NC attenuated the expression of osteoclast marker genes including cathepsin K, D2, calcitonin receptor, NFATc1, and TRAP. Further, NC inhibited RANKL-activated NF-κB and NFATc1 signalling pathways. In vivo study revealed that NC abrogated oestrogen deficiency-induced bone loss in ovariectomized mice. Histological analysis showed that the number of osteoclasts was significantly lower in NC-treated groups. Collectively, our data demonstrate that NC suppressed osteoclastogenesis and prevented OVX-induced bone loss by inhibiting RANKL-induced NF-κB and NFATc1 signalling pathways. NC may be a natural and novel treatment for osteoclast-related bone lytic diseases.
Research Centre for Regenerative Medicine, Department of Trauma Orthopedic and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi, 530021, China.|School of Pathology and Laboratory Medicine, The University of Western Australia, Perth WA 6009, Australia.
Qian
Q
Liu
Research Centre for Regenerative Medicine, Department of Trauma Orthopedic and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi, 530021, China.|Department of Orthopedics, The First Affiliated Hospital of Gaungxi Medical University, 22 Shuangyong Road, Guangxi, 530022, China.
Tao
T
Wang
School of Pathology and Laboratory Medicine, The University of Western Australia, Perth WA 6009, Australia.
Lin
L
Zhou
Research Centre for Regenerative Medicine, Department of Trauma Orthopedic and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi, 530021, China.|School of Pathology and Laboratory Medicine, The University of Western Australia, Perth WA 6009, Australia.|School of Pharmacology, Guangxi Medical University, Guangxi, 530021, China.
Fangming
F
Song
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
Program of Nutrition and Bone &Joint Health, Nestlé R&D (China) Ltd. Building 5, No. 5 Dijin Road, Haidian District, Beijing, 100095, China.
Hao Tian
HT
Feng
Research Centre for Regenerative Medicine, Department of Trauma Orthopedic and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi, 530021, China.
Xi Xi
XX
Lin
Centre for Orthopaedic Research, School of Surgery, The University of Western Australia, Perth WA 6009, Australia.
Zhen
Z
Lin
School of Pathology and Laboratory Medicine, The University of Western Australia, Perth WA 6009, Australia.
Jin Bo
JB
Yuan
School of Pathology and Laboratory Medicine, The University of Western Australia, Perth WA 6009, Australia.
Jennifer
J
Tickner
School of Pharmacology, Guangxi Medical University, Guangxi, 530021, China.
Hua Gang
HG
Liu
Centre for Orthopaedic Research, School of Surgery, The University of Western Australia, Perth WA 6009, Australia.
Ming Hao
MH
Zheng
Research Centre for Regenerative Medicine, Department of Trauma Orthopedic and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi, 530021, China.|School of Pathology and Laboratory Medicine, The University of Western Australia, Perth WA 6009, Australia.
Jiake
J
Xu
Research Centre for Regenerative Medicine, Department of Trauma Orthopedic and Hand Surgery, The First Affiliated Hospital of Guangxi Medical University, Guangxi, 530021, China.|Guangxi Key Laboratory of Regenerative Medicine, Guangxi Medical University, Guangxi, 530021, China.
Jin Min
JM
Zhao
D000818:Animals; D053119:Benzophenanthridines / Q000494:pharmacology*; D001862:Bone Resorption / Q000378:metabolism / Q000473:pathology / Q000517:prevention & control*; D002454:Cell Differentiation / Q000187:drug effects*; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D051379:Mice; D050778:NFATC Transcription Factors / Q000378:metabolism*; D010010:Osteoclasts / Q000378:metabolism* / Q000473:pathology; D015398:Signal Transduction / Q000187:drug effects*; D000071681:Tartrate-Resistant Acid Phosphatase / Q000096:biosynthesis
D053119:Benzophenanthridines; D050778:NFATC Transcription Factors; C494005:Nfatc1 protein, mouse; C013615:nitidine; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase