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Molecular mechanisms of bone formation and absorption in the ankle joint of adjuvant arthritic rats

佐剂性关节炎大鼠踝关节骨形成和吸收的分子机制

基本信息

批准号：
14571737
负责人：
IIJIMA Tadahiko
金额：
$ 1.79万
依托单位：
Kyushu University
依托单位国家：
日本
项目类别：
Grant-in-Aid for Scientific Research (C)
财政年份：
2002
资助国家：
日本
起止时间：
2002 至 2003
项目状态：
已结题

项目摘要

Adjuvant arthritis (AA), an experimental model of rheumatoid arthritis, Is characterized by the infiltration of mononuclear cells in synovial tissues, pannus formation, articular cartilage erosion, bone absorption, and periosteal bone formation of ankle joints. The molecular mechanism of bone absorption and formation in the Inflamed tissues of AA rats was of particular interest in this investigation. The following findings were published or will soon be published.1) The sensory nerves may be related to a remission of the synovial inflammation and that the sensory nerves and the macrophages can be involves in osteophyte formation. It seems highly probable that a sensory innervation will influence the inflammatory processes and these, in turn, will affect the formation of osteophytes, though a possible direct effect of sensory nerves on the osteoblasts can not be excluded In the ankle joints of AA rats (Wu et al., 2002).2) CGRP being released from newly sprouted sensory nerve fibers after adjuvant injection may be involved in a remission of the synovial inflammation via regulation of Th1/Th2 balance. This appears to be supported by recent studies which have demonstrated the characteristic increase of Th1 cytokine expression in the early stage and that of Th2 in later stages of AA. Our observation strongly suggested the presence of the anti-inflammatory action of sensory nerves In rats with AA (Wu et al., 2004).3) MIP-1α may be involved in the migration of osteoclast progenitors to the distal tibia as well as in osteoclastogenesis in AA rats. Migrated osteoclast progenitors are thought to be efficiently differentiate into osteoclasts in response to RANKL expressed by the aggregates of oseoclast-like cells under the influence of the MIP-1α. Such positive-feedback regulation of osteoclastogenesis could result in the highest recruitment of active osteoclasts In the area of marked bone destruction (Toh et al., In press).

佐剂性关节炎（AA）是类风湿关节炎的一种实验模型，其特征是滑膜组织中单个核细胞浸润，形成鞘膜，关节软骨侵蚀，骨吸收，踝关节骨膜骨形成。AA大鼠炎症组织骨吸收和骨形成的分子机制是本研究的重点。以下研究结果已发表或即将发表。1)感觉神经可能与滑膜炎症的缓解有关，感觉神经和巨噬细胞可能参与骨赘的形成。感觉神经支配很可能会影响炎症过程，而炎症过程反过来又会影响骨赘的形成，尽管在AA大鼠的踝关节中不能排除感觉神经对成骨细胞的直接影响（Wu et al., 2002）。2)佐剂注射后新生感觉神经纤维释放CGRP可能通过调节Th1/Th2平衡参与滑膜炎症的缓解。这似乎得到了最近研究的支持，这些研究表明，在AA的早期和晚期，Th1细胞因子表达的特征性增加。我们的观察强烈提示AA大鼠的感觉神经存在抗炎作用（Wu et al., 2004）。3) MIP-1α可能参与了AA大鼠破骨细胞祖细胞向胫骨远端迁移以及破骨细胞的形成。迁移的破骨细胞祖细胞被认为在MIP-1α的影响下，对破骨细胞样细胞聚集表达的RANKL作出反应，从而有效地分化为破骨细胞。这种对破骨细胞生成的正反馈调节可能导致在明显的骨破坏区域中活性破骨细胞的最高募集（Toh等，in press）。