Nerve growth factor, Its role in regulation of an abnormal bone remodeling in local inflammation.

神经生长因子，其在调节局部炎症异常骨重塑中的作用。

• 批准号: 11671804
• 负责人: IIJIMA Tadahiko
• 金额: $ 2.5万
• 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: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11671804/
• 关键词: inflammation; bone resorption; bone formation; adjuvant arthritis; nerve growth factor; inflammatory cells; immunohistochemistry; sensory innervation; アジュバント関節炎

To study the role of nerve growth factor (NGF) in local inflammation, we investigated the expression of NGF and its receptors, trkA and p75, in the ankle joints of adjuvant-induced arthritic rats. Infiltrated mononuclear cells revealed a positive immunoreactivity for NGF and trkA ; they were also positive for immunostaining for W3/25 and ED1, which mainly stain T cells and macrophages, respectively. It seems that infiltrated mononuclear cells may secrete NGF in an autocrine or paracrinemanner in the inflamed synovium. At weeks 2 to 4, dense meshworks of p75-positive nerve fibers with numerous terminal varicosities were observed in the visinity of the tibial and fibular metaphysis periosteum. Abnormal bone formation, forming bone knots, could be observed adjacentto the nerve plexuses at 3 weeks after the adjuvantinjection. The double-immunofluorescencestaining method using p75 and GAP-43 or CGRP antibodies indicated that a sprout of CGRP-positive sensory nerves was accelerated by NGF and that bone formation forming bone knots was activated by CGRP in adjuvant-inducedarthritic rats. Unilateral axotomy by resection of the sciatic nerve before adjuvant injection resulted reduction of the response to the adjuvant injection ; that is, in axotomized rats, less serious inflamation and bone knot formation were induced by adjuvant injection as compared with those in non-axotomized rats. An upregulation of NGF in the mononuclear cells in the inflamed synovium and an increase in density of the synovial sensory nerves may be involved in the development of adjuvant arthritis in rats.

为探讨神经生长因子(NGF)在局部炎症中的作用，我们观察了NGF及其受体TrkA和p75在佐剂性关节炎大鼠踝关节中的表达。浸润的单个核细胞对NGF和TrkA呈阳性反应，对W3/25和ED1也呈阳性反应，分别主要染色T细胞和巨噬细胞。浸润性单个核细胞可能在炎症滑膜的自分泌或旁分泌中分泌NGF。2~4周时，在胫骨和腓骨干干端骨膜粘连处可见致密的p75阳性神经纤维网络，并可见大量终末曲张。注射佐剂后3周，神经丛附近可见异常骨形成，形成骨结。用p75和GAP-43或CGRP抗体进行免疫荧光双标记法显示，NGF促进了CGRP阳性感觉神经的萌发，CGRP激活了骨形成骨结节。在注射佐剂前切断坐骨神经的一侧坐骨神经切断导致对注射佐剂的反应降低，即在轴突切断的大鼠中，佐剂注射引起的炎症和骨结形成的程度比非轴突切断的大鼠轻。炎症滑膜单个核细胞NGF表达上调和滑膜感觉神经密度增加可能参与了大鼠佐剂性关节炎的发生发展。

项目成果

Z.Wu et al.: "Immunohistochemical study of NGF and its receptorsin the synovial membrane of the ankle joint of adjuvant-inducedarthritic rats."Histochemistry and Cell Biology. 114. 453-459 (2000)

Z.Wu 等人：“佐剂诱导关节炎大鼠踝关节滑膜中 NGF 及其受体的免疫组织化学研究。”组织化学和细胞生物学。

Z.Wu et al.: "Immunohistochemical study of NGF and its receptors in the synovial membrane of the ankle joint of adjuvant-induced arthritic rats."Histochemistry and Cell Biology. 114. 453-459 (2000)

Z.Wu 等人：“佐剂诱发关节炎大鼠踝关节滑膜中 NGF 及其受体的免疫组织化学研究。”组织化学和细胞生物学。