The effect of CCL3 and CCR1 in bone remodeling induced by mechanical loading during orthodontic tooth movement in mice
The effect of CCL3 and CCR1 in bone remodeling induced by mechanical loading during orthodontic tooth movement in mice
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DOI：
10.1016/j.bone.2012.09.036
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发表时间：
2013-01-01
期刊：
影响因子：
4.1
通讯作者：
da Silva, Tarcilia A.
中科院分区：
文献类型：
--
作者：
de Albuquerque Taddei, Silvana R.;Queiroz-Junior, Celso M.;da Silva, Tarcilia A.
骨重建受机械负荷和炎症介质的影响，包括趋化因子。趋化因子(C-C基序)配体3(CCL3)通过与破骨细胞和成骨细胞上表达的C-C趋化因子受体1和5(CCR1和CCR5)结合而参与骨重建。我们的研究小组先前已经证明，CCR5下调机械负荷诱导的骨吸收。因此，本研究旨在探讨CCR1和CCL3在小鼠正畸牙移动过程中机械负荷引起的骨改建中的作用。我们的结果表明，CCL3(-/-)和CCR1(-/-)小鼠以及经CCR5和CCR1拮抗剂Met-RANTES处理的动物的骨重建显著减少。CCL3(-/-)组和Met-RANTES组小鼠牙周组织中核因子kappaB受体激活剂(RANK)及其配体RANKL、肿瘤坏死因子α(TNF-α)和RANKL/OPG比值的mRNA水平均降低。MET-RANTES治疗还可降低组织蛋白酶K和金属蛋白酶13(MMP13)的水平。CCL3(-/-)和Met-RANTES处理组小鼠成骨细胞标志物RUNX2和Periostin表达降低，骨钙素(OCN)表达增强。综上所述，这些发现表明，CCR1在正畸牙齿移动过程中机械负荷引起的骨重建中起关键作用，这些作用至少部分依赖于CCL3。(C)2012 Elsevier Inc.保留所有权利。
Bone remodeling is affected by mechanical loading and inflammatory mediators, including chemokines. The chemokine (C-C motif) ligand 3 (CCL3) is involved in bone remodeling by binding to C-C chemokine receptors 1 and 5 (CCR1 and CCR5) expressed on osteoclasts and osteoblasts. Our group has previously demonstrated that CCR5 down-regulates mechanical loading-induced bone resorption. Thus, the present study aimed to investigate the role of CCR1 and CCL3 in bone remodeling induced by mechanical loading during orthodontic tooth movement in mice. Our results showed that bone remodeling was significantly decreased in CCL3(-/-) and CCR1(-/-) mice and in animals treated with Met-RANTES (an antagonist of CCR5 and CCR1). mRNA levels of receptor activator of nuclear factor kappa-B (RANK), its ligand RANKL, tumor necrosis factor alpha (TNF-alpha) and RANKL/osteoprotegerin (OPG) ratio were diminished in the periodontium of CCL3(-/-) mice and in the group treated with Met-RANTES. Met-RANTES treatment also reduced the levels of cathepsin K and metalloproteinase 13 (MMP13). The expression of the osteoblast markers runt-related transcription factor 2 (RUNX2) and periostin was decreased, while osteocalcin (OCN) was augmented in CCL3(-/-) and Met-RANTES-treated mice. Altogether, these findings show that CCR1 is pivotal for bone remodeling induced by mechanical loading during orthodontic tooth movement and these actions depend, at least in part, on CCL3. (C) 2012 Elsevier Inc. All rights reserved.