Mechanisms involved in regulation of osteoclastic differentiation by mechanical stress-loaded osteoblasts

被引:40
作者
Kaneuji, Takeshi [2 ,3 ]
Ariyoshi, Wataru [3 ]
Okinaga, Toshinori [3 ]
Toshinaga, Akihiro [3 ]
Takahashi, Tetsu [1 ,2 ]
Nishihara, Tatsuji [1 ,3 ]
机构
[1] Kyushu Dent Coll, Oral Biores Ctr, Kokurakita Ku, Kitakyushu, Fukuoka 8038580, Japan
[2] Kyushu Dent Coll, Div Oral & Maxillofacial Reconstruct Surg, Dept Oral & Maxillofacial Surg, Kokurakita Ku, Kitakyushu, Fukuoka 8038580, Japan
[3] Kyushu Dent Coll, Div Infect & Mol Biol, Dept Hlth Promot, Kokurakita Ku, Kitakyushu, Fukuoka 8038580, Japan
关键词
Mechanical stress; Osteoclastogenesis; Non-canonical Wnt pathway; Osteoprotegerin; NF-KAPPA-B; PERIODONTAL-LIGAMENT CELLS; RECEPTOR ACTIVATOR; RANKL EXPRESSION; PATHWAYS; KINASE; STRAIN; OSTEOPROTEGERIN; INHIBITION; OSTEOCYTES;
D O I
10.1016/j.bbrc.2011.03.128
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Mechanical stress is known to be important for regulation of bone turnover, though the detailed mechanisms are not fully understood. In the present study, we examined the effect of mechanical stress on osteoblasts using a novel compression model. Mouse osteoblastic MC3T3-E1 cells were embedded in three-dimensional (3D) gels and cultured with continuous compressive force (0-10.0 g/cm(2)) for 48 h, and the conditioned medium were collected. RAW264.7 cells were then incubated with the conditioned medium for various times in the presence of receptor activator of nuclear factor-kappa B ligand (RANKL). Conditioned medium was found to inhibit the differentiation of RAW264.7 cells into osteoclasts induced by RANKL via down-regulation of the expression of tumor necrosis factor receptor-associated factor 6 (TRAF6), phosphorylation of I kappa B alpha, and nuclear translocation of p50 and p65. Interestingly, the conditioned medium also had a high level of binding activity to RANKL and blocked the binding of RANK to RANKL. Furthermore, the binding activity of conditioned medium to RANKL was reduced when the 3D gel was supplemented with KN-93, an inhibitor of non-canonical Wnt/Ca2+ pathway. In addition, expression level of osteoprotegerin (OPG) mRNA was increased in time- and force-dependent manners, and remarkably suppressed by KN-93. These results indicate that osteoblastic cells subjected to mechanical stress produce OPG, which binds to RANKL Furthermore, this binding activity strongly inhibited osteoclastogenesis through suppression of TRAF6 and the nuclear factor-kappa B (NF-kappa B) signaling pathway, suggesting that enhancement of OPG expression induced by mechanical stress is dependent on non-canonical Wnt/Ca2+ pathway. 2011 Elsevier Inc. All rights reserved.
引用
收藏
页码:103 / 109
页数:7
相关论文
共 38 条
[11]   Molecular regulation of mechanotransduction [J].
Iqbal, J ;
Zaidi, M .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2005, 328 (03) :751-755
[12]   Inhibition of RANK Expression and Osteoclastogenesis by TLRs and IFN-γ in Human Osteoclast Precursors [J].
Ji, Jong-Dae ;
Park-Min, Kyung-Hyun ;
Shen, Zenxin ;
Fajardo, Roberto J. ;
Goldring, Steven R. ;
McHugh, Kevin P. ;
Ivashkiv, Lionel B. .
JOURNAL OF IMMUNOLOGY, 2009, 183 (11) :7223-7233
[13]   Activation of NF-κB is involved in the survival of osteoclasts promoted by interleukin-1 [J].
Jimi, E ;
Nakamura, I ;
Ikebe, T ;
Akiyama, S ;
Takahashi, N ;
Suda, T .
JOURNAL OF BIOLOGICAL CHEMISTRY, 1998, 273 (15) :8799-8805
[14]   Periodontal ligament cells under mechanical stress induce osteoclastogenesis by receptor activator of nuclear factor κB ligand up-regulation via prostaglandin E2 synthesis [J].
Kanzaki, H ;
Chiba, M ;
Shimizu, Y ;
Mitani, H .
JOURNAL OF BONE AND MINERAL RESEARCH, 2002, 17 (02) :210-220
[15]  
KOOK SH, 2009, J CELL BIOCHEM, V106, P1009
[16]   Mechanical regulation of osteoclastic genes in human osteoblasts [J].
Kreja, Ludwika ;
Liedert, Astrid ;
Hasni, Sofia ;
Claes, Lutz ;
Ignatius, Anita .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2008, 368 (03) :582-587
[17]   Bone marrow cell differentiation induced by mechanically damaged osteocytes in 3D gel-embedded culture [J].
Kurata, K ;
Heino, TJ ;
Higaki, H ;
Väänänen, HK .
JOURNAL OF BONE AND MINERAL RESEARCH, 2006, 21 (04) :616-625
[18]   Maslinic Acid Suppresses Osteoclastogenesis and Prevents Ovariectomy-Induced Bone Loss by Regulating RANKL-Mediated NF-κB and MAPK Signaling Pathways [J].
Li, Chenghai ;
Yang, Zhengfeng ;
Li, Zhenxi ;
Ma, Yu ;
Zhang, Lipeng ;
Zheng, Chunbing ;
Qiu, Wenwei ;
Wu, Xian ;
Wang, Xiu ;
Li, Hui ;
Tang, Jie ;
Qian, Min ;
Li, Dali ;
Wang, Ping ;
Luo, Jian ;
Liu, Mingyao .
JOURNAL OF BONE AND MINERAL RESEARCH, 2011, 26 (03) :644-656
[19]   Signal transduction pathways involved in mechanotransduction in bone cells [J].
Liedert, Astrid ;
Kaspar, Daniela ;
Blakytny, Robert ;
Claes, Lutz ;
Ignatius, Anita .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2006, 349 (01) :1-5
[20]   Estrogen receptor and Wnt signaling interact to regulate early gene expression in response to mechanical strain in osteoblastic cells [J].
Liedert, Astrid ;
Wagner, Liane ;
Seefried, Lothar ;
Ebert, Regina ;
Jakob, Franz ;
Ignatius, Anita .
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2010, 394 (03) :755-759