Baicalin positively regulates osteoclast function by activating MAPK/Mitf signalling.
Activation of osteoblasts in bone formation and osteoclasts in bone resorption is important during the bone fracture healing process. There has been a long interest in identifying and developing a natural therapy for bone fracture healing. In this study, we investigated the regulation of osteoclast differentiation by baicalin, which is a natural molecule extracted from Eucommiaulmoides (small tree native to China). It was determined that baicalin enhanced osteoclast maturation and bone resorption activity in a dose-dependent manner. Moreover, this involves the activation of MAPK, increased Mitf nuclear translocation and up-regulation of downstream osteoclast-related target genes expression. The baicalin-induced effect on osteoclast differentiation can be mimicked by specific inhibitors of p-ERK (U0126) and the Mitf-specific siRNA, respectively. Protein-ligand docking prediction identified that baicalin might bind to RANK, which is the upstream receptor of p-ERK/Mitf signalling in osteoclasts. This indicated that RANK might be the binding target of baicalin. In sum, our findings revealed baicalin increased osteoclast maturation and function via p-ERK/Mitf signalling. In addition, the results suggest that baicalin can potentially be used as a natural product for the treatment of bone fracture.
School of Life Science and Biopharmacy, Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou, China.
Li
L
Lu
School of Life Science and Biopharmacy, Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou, China.
Li
L
Rao
Guangdong Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, China.
Huanhuan
H
Jia
School of Life Science and Biopharmacy, Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou, China.
Jun
J
Chen
School of Life Science and Biopharmacy, Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou, China.
Xingyan
X
Lu
School of Life Science and Biopharmacy, Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou, China.
Guozhu
G
Yang
School of Life Science and Biopharmacy, Guangdong Key Laboratory of Pharmaceutical Bioactive Substances, Guangdong Pharmaceutical University, Guangzhou, China.|Guangdong Key Laboratory of Laboratory Animals, Guangdong Laboratory Animals Monitoring Institute, Guangzhou, China.
Qingnan
Q
Li
Stem Cell and Regeneration Thematic Research Program, School of Biomedical Sciences, The Chinese University of Hong Kong, Shatin, Hong Kong SAR, China.
Kenneth Ka Ho
KKH
Lee
Zhujiang Hospital of Southern Medical University, Guangzhou, China.
Li
L
Yang
D000818:Animals; D001862:Bone Resorption / Q000235:genetics / Q000503:physiopathology; D002070:Butadienes / Q000008:administration & dosage; D002454:Cell Differentiation / Q000187:drug effects; D005419:Flavonoids / Q000008:administration & dosage*; D050723:Fractures, Bone / Q000188:drug therapy* / Q000235:genetics / Q000503:physiopathology; D006801:Humans; D048369:MAP Kinase Kinase 1 / Q000037:antagonists & inhibitors / Q000235:genetics*; D051379:Mice; D051739:Microphthalmia-Associated Transcription Factor / Q000037:antagonists & inhibitors / Q000235:genetics*; D009570:Nitriles / Q000008:administration & dosage; D010010:Osteoclasts / Q000187:drug effects / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics; D011485:Protein Binding; D000067996:RAW 264.7 Cells; D053246:Receptor Activator of Nuclear Factor-kappa B / Q000235:genetics*; D015398:Signal Transduction / Q000187:drug effects
D002070:Butadienes; D005419:Flavonoids; C497234:MITF protein, human; D051739:Microphthalmia-Associated Transcription Factor; D009570:Nitriles; D053246:Receptor Activator of Nuclear Factor-kappa B; C113580:U 0126; C038044:baicalin; D048369:MAP Kinase Kinase 1
MAPK/Mitf signalling; baicalin; bone fracture healing; osteoclast