Heinrich J, Bsoul S, Barnes J, Woodruff K, Abboud S
Department of Orthodontics, University of Texas Health Science Center, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA.
Arch Oral Biol. 2005 Oct;50(10):897-908. doi: 10.1016/j.archoralbio.2005.02.007. Epub 2005 Apr 9.
During tooth eruption, osteoclast-mediated bone resorption predominates in alveolar bone along the occlusal surface rather than in bone basal to the tooth. CSF-1, RANKL and OPG, regulatory molecules essential for osteoclastogenesis, are expressed during eruption. However, it is unclear if these cytokines exhibit an expression pattern that correlates with sites of osteoclastogenesis in vivo. To address this issue, mouse mandibles, isolated from 1 to 14 days postnatal, were analysed for osteoclast activity using tartrate-resistant acid phosphatase (TRAP) staining as well as colony-stimulating factor-1 (CSF-1), receptor activator of nuclear factor-kappa B ligand (RANKL) and osteoprotegerin (OPG) mRNA expression using in situ hybridisation. Results showed that CSF-1, RANKL and OPG are expressed in a distinct temporal and spatial manner. In the occlusal region, osteoclast activity was maximal at day 5 and correlated with a relative high expression of CSF-1 and RANKL compared to OPG. In basal bone at this time point, osteoclast activity decreased despite persistent CSF-1 expression and was associated with increased expression of OPG compared to RANKL. By day 8, osteoclastogenesis declined and correlated with upregulation of OPG at the occlusal and basal regions, with this effect continuing throughout eruption. These findings suggest that the spatiotemporal pattern and relative abundance of CSF-1, RANKL and OPG during eruption are key determinants of site-specific osteoclast activity in bone surrounding the tooth. Targeting these cytokines to specific regions in alveolar bone may provide a mechanism for regulating osteoclastogenesis in dental disorders associated with altered tooth eruption.
在牙齿萌出过程中，破骨细胞介导的骨吸收在牙槽骨沿咬合面处占主导，而非在牙齿基部的骨中。集落刺激因子-1（CSF-1）、核因子κB受体活化因子配体（RANKL）和骨保护素（OPG）是破骨细胞生成所必需的调节分子，在牙齿萌出期间表达。然而，尚不清楚这些细胞因子是否表现出与体内破骨细胞生成部位相关的表达模式。为解决这一问题，对出生后1至14天分离的小鼠下颌骨进行分析，使用抗酒石酸酸性磷酸酶（TRAP）染色检测破骨细胞活性，并使用原位杂交检测集落刺激因子-1（CSF-1）、核因子κB受体活化因子配体（RANKL）和骨保护素（OPG）mRNA表达。结果表明，CSF-1、RANKL和OPG以独特的时间和空间方式表达。在咬合区域，破骨细胞活性在第5天达到最大值，与CSF-1和RANKL相对于OPG的相对高表达相关。在这个时间点的基部骨中，尽管CSF-1持续表达，但破骨细胞活性下降，并且与OPG相对于RANKL的表达增加相关。到第8天，破骨细胞生成减少，与咬合和基部区域OPG的上调相关，这种作用在整个萌出过程中持续存在。这些发现表明，牙齿萌出期间CSF-1、RANKL和OPG的时空模式和相对丰度是牙齿周围骨中位点特异性破骨细胞活性的关键决定因素。将这些细胞因子靶向牙槽骨的特定区域可能为调节与牙齿萌出改变相关的牙齿疾病中的破骨细胞生成提供一种机制。
