Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang Key Laboratory for Agro-Food Processing; Zhejiang Engineering Center for Food Technology and Equipment, Zhejiang University, Hangzhou, China
Zhenlei Zhao
Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang Key Laboratory for Agro-Food Processing; Zhejiang Engineering Center for Food Technology and Equipment, Zhejiang University, Hangzhou, China
Yanpei Gu
Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang Key Laboratory for Agro-Food Processing; Zhejiang Engineering Center for Food Technology and Equipment, Zhejiang University, Hangzhou, China
Jianxin Han
Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang Key Laboratory for Agro-Food Processing; Zhejiang Engineering Center for Food Technology and Equipment, Zhejiang University, Hangzhou, China
Keqiang Ye
Department of Pathology and Laboratory Medicine, Emory University School of Medicine, Atlanta, United States
Department of Food Science and Nutrition, College of Biosystems Engineering and Food Science, Zhejiang Key Laboratory for Agro-Food Processing; Zhejiang Engineering Center for Food Technology and Equipment, Zhejiang University, Hangzhou, China
Imbalances in bone formation and resorption cause osteoporosis. Mounting evidence supports that brain-derived neurotrophic factor (BDNF) implicates in this process. 7,8-Dihydroxyflavone (7,8-DHF), a plant-derived small molecular TrkB agonist, mimics the functions of BDNF. We show that both BDNF and 7,8-DHF promoted the proliferation, osteogenic differentiation, and mineralization of MC3T3-E1 cells. These effects might be attributed to the activation of the Wnt/β-catenin signaling pathway as the expression of cyclin D1, phosphorylated-glycogen synthase kinase-3β (p-GSK3β), β-catenin, Runx2, Osterix, and osteoprotegerin (OPG) was all significantly up-regulated. Knockdown of β-catenin restrained the up-regulation of Runx2 and Osterix stimulated by 7,8-DHF. In particular, blocking TrkB by its specific inhibitor K252a suppressed 7,8-DHF-induced osteoblastic proliferation, differentiation, and expression of osteoblastogenic genes. Moreover, BDNF and 7,8-DHF repressed osteoclastic differentiation of RAW264.7 cells. The transcription factor c-fos and osteoclastic genes such as tartrate-resistant acid phosphatase (TRAP), matrix metalloprotein-9 (MMP-9), Adamts5 were inhibited by 7,8-DHF. More importantly, 7,8-DHF attenuated bone loss, improved trabecular microarchitecture, tibial biomechanical properties, and bone biochemical indexes in an ovariectomy (OVX) rat model. The current work highlights the dual regulatory effects that 7,8-DHF exerts on bone remodeling.
