Dual effects of baicalin on osteoclast differentiation and bone resorption

被引:20
作者
Lu, Xuanyuan [1 ]
He, Wei [1 ]
Yang, Wanlei [1 ]
Li, Jianlei [1 ]
Han, Weiqi [1 ]
Liu, Qian [2 ]
Zhang, Tan [1 ]
Jiang, Jiawei [1 ]
Qin, An [3 ]
Qian, Yu [1 ]
机构
[1] Zhejiang Univ, Sch Med, Shaoxing Hosp, Dept Orthopaed,Shaoxing Peoples Hosp, Shaoxing, Zhejiang, Peoples R China
[2] Guangxi Med Univ, Res Ctr Regenerat Med, Guangxi, Peoples R China
[3] Shanghai Jiao Tong Univ, Sch Med, Shanghai Peoples Hosp 9, Dept Orthoped,Shanghai Key Lab Orthoped Implants, Shanghai, Peoples R China
基金
中国国家自然科学基金;
关键词
apoptosis; baicalin; differentiation; dual effects; osteoclasts; CANCER CELLS; APOPTOSIS; FLAVONOIDS; INSIGHTS;
D O I
10.1111/jcmm.13785
中图分类号
Q2 [细胞生物学];
学科分类号
071009 ; 090102 ;
摘要
Osteoclasts (OC) are critical cells responsible for many bone diseases such as osteoporosis. It is of great interest to identify agents that can regulate the activity of OC to treat osteolytic bone diseases. In this study, we found that baicalin exerted a two-way regulatory effect on OC in a concentration-dependent manner invitro and invivo. In detail, baicalin at a low concentration (below 1 mu mol/L) enhanced OC differentiation and bone resorption, but baicalin at a high concentration (above 2 mu mol/L) exhibited inhibitory effects on OC. We demonstrated that baicalin at low concentrations enhanced the mitogen-activated protein kinase (MAPK) (ERK) signalling pathway and activated c-Fos and NFATc1 expression, and thus enhanced gene expression, OC differentiation and bone resorption. However, baicalin at higher levels not only suppressed ERK phosphorylation and c-fos and NFATc1 expression, but also altered the expression of apoptosis-related proteins, and therefore inhibiting OC function. This dual effect was further verified in an LPS-induced mouse calvarial osteolysis model, evidenced by enhanced osteolysis at a lower concentration but reduced bone loss at a higher concentration. Overall, our findings indicate that baicalin exerts dose-dependent effects on OC formation and function. Therefore, caution should be applied when using baicalin to treating OC-related bone diseases.
引用
收藏
页码:5029 / 5039
页数:11
相关论文
共 32 条
  • [1] Al Mamun MA, 2015, BIOL RES, V48, DOI [10.1186/s40659-015-0043-6, 10.1186/S40659-015-0043-6]
  • [2] Estrogen-dependent and C-C chemokine receptor-2-dependent pathways determine osteoclast behavior in osteoporosis
    Binder, Nikolaus B.
    Niederreiter, Birgit
    Hoffmann, Oskar
    Stange, Richard
    Pap, Thomas
    Stulnig, Thomas M.
    Mack, Matthias
    Erben, Reinhold G.
    Smolen, Josef S.
    Redlich, Kurt
    [J]. NATURE MEDICINE, 2009, 15 (04) : 417 - 424
  • [3] Osteoclast differentiation and activation
    Boyle, WJ
    Simonet, WS
    Lacey, DL
    [J]. NATURE, 2003, 423 (6937) : 337 - 342
  • [4] Baicalin Alleviates Lipopolysaccharide-Induced Liver Inflammation in Chicken by Suppressing TLR4-Mediated NF-κB Pathway
    Cheng, Ping
    Wang, Tong
    Li, Wei
    Muhammad, Ishfaq
    Wang, He
    Sun, Xiaoqi
    Yang, Yuqi
    Li, Jiarui
    Xiao, Tianshi
    Zhang, Xiuying
    [J]. FRONTIERS IN PHARMACOLOGY, 2017, 8
  • [6] Dual Effect of Cyanidin on RANKL-Induced Differentiation and Fusion of Osteoclasts
    Dou, Ce
    Li, Jianmei
    Kang, Fei
    Cao, Zhen
    Yang, Xiaochao
    Jiang, Hong
    Yang, Bo
    Xiang, Junyu
    Xu, Jianzhong
    Dong, Shiwu
    [J]. JOURNAL OF CELLULAR PHYSIOLOGY, 2016, 231 (03) : 558 - 567
  • [7] Advances in osteoclast biology: old findings and new insights from mouse models
    Edwards, James R.
    Mundy, Gregory R.
    [J]. NATURE REVIEWS RHEUMATOLOGY, 2011, 7 (04) : 235 - 243
  • [8] Antitumor effects of baicalin on ovarian cancer cells through induction of cell apoptosis and inhibition of cell migration in vitro
    Gao, Chen
    Zhou, Yinglu
    Li, Huatao
    Cong, Xia
    Jiang, Zhongling
    Wang, Xin
    Cao, Rongfeng
    Tian, Wenru
    [J]. MOLECULAR MEDICINE REPORTS, 2017, 16 (06) : 8729 - 8734
  • [9] Osteoclast Activity and Subtypes as a Function of Physiology and Pathology-Implications for Future Treatments of Osteoporosis
    Henriksen, K.
    Bollerslev, J.
    Everts, V.
    Karsdal, M. A.
    [J]. ENDOCRINE REVIEWS, 2011, 32 (01) : 31 - 63
  • [10] B cells and osteoblast and osteoclast development
    Horowitz, MC
    Bothwell, ALM
    Hesslein, DGT
    Pflugh, DL
    Schatz, DG
    [J]. IMMUNOLOGICAL REVIEWS, 2005, 208 : 141 - 153