歯の移動時におけるケモカインの発現に関する検討

Chemokines are a group of cytokines that form a large family of structurally related proteins and are chemotactically active for specific types of leukocytes. Recently, various biological effects of chemokine such as angiogenesis, immune response and cancer metastasis were reported, in addition to chemotactic activity for leukocytes. The objective of this study was to analyze the expression of chemokines in the periodontal tissue remodeling during experimental tooth movement. Tooth movement was performed by the elastic band insertion between the upper first and second molars of 7 weeks-old male Sprague-Dawley rats according to the method of Waldo. The animals were sacrificed at 12 hours, 1, 2, 3, 4 and 7 days after the placement of elastic bands. The rats without elastic bands were used as controls. Reverse transcription polymerase chain reaction (RTPCR) analysis using specific primers for chemokines and its receptors revealed that the expression of Macrophage inflammatory protein-1 alpha (MIP-1α) and its receptors (CCR1, CCR5), and that of Stromal cell-derived factor-1 (SDF-1) and its receptor CXCR4 were increased in the periodontal tissue during tooth movement. In addition, immunohistochemical staining was carried out using paraffin embedded sections to examine the localization of these chemokines and receptors. MIP-1α expression was observed in the pressure side of periodontal ligament (PDL) fibroblast at 1 and 2 days after orthodontic force application. On the other hand, CCR5 expression was observed in PDL fibroblast and osteoblast, and a high level of expression could be observed at 3 days. SDF-1 was expressed by PDL fibroblast and osteoblast, and a maximum expression could be found at 3 days. CXCR4 positive cells were detected in the bone marrow of alveolar bone, and the number of these cells were increased corresponding to tooth movement. Furthermore, to analyze the effect of MIP-1α toward osteoclast, in vitro experiment was performed by means of rabbit unfractionated bone cell cultures. As a result, MIP-1α promoted osteoclast formation, activation and chemotacitc activity, and Osteoprotegerin (OPG) blocked MIP-1α-stimulated osteoclast formation and activation. These results suggest that MIP-1α induces osteoblast RANK ligand expression via CCR5, consequently enhances osteoclastic bone resorption, and that SDF-1 promotes recruitment of CXCR4 positive cells including endothelial progenitor cells and osteoclast precursors. Therefore, these chemokines and receptors may be involved in periodontal tissue remodeling.

公開日:2010年1月24日で登録したコンテンツは、国立情報学研究所において電子化したものです。