Possible involvement of the vascular endothelial growth factor-Flt-1-focal adhesion kinase pathway in chemotaxis and the cell proliferation of osteoclast precursor cells in arthritic joints
Possible involvement of the vascular endothelial growth factor-Flt-1-focal adhesion kinase pathway in chemotaxis and the cell proliferation of osteoclast precursor cells in arthritic joints
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DOI：
10.4049/jimmunol.168.11.5824
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发表时间：
2002-06-01
影响因子：
4.4
通讯作者：
Iwamoto, Y
中科院分区：
文献类型：
--
作者：
Matsumoto, Y;Tanaka, K;Iwamoto, Y
血管内皮生长因子（VEGF）在炎症性关节疾病（包括血管生成和滑膜炎）的发病机制中起着至关重要的作用。类风湿性关节炎是一种慢性炎症性疾病，其特征是进行性滑膜炎和随后由破骨细胞介导的骨破坏。在这项研究中，我们使用原始细胞和佐剂诱导的大鼠关节炎来研究VEGF对OC前体细胞（pOCs）的影响。关节炎关节的OCs和pOCs表达VEGF和VEGF受体I型（Flt-1）。Raw细胞也表达Flt-1， VEGF处理刺激了Raw细胞的趋化性、细胞增殖、Flt-1与局灶黏附激酶（FAK）的关联以及FAK的酪氨酸磷酸化。FAK的酪氨酸磷酸化也在佐剂诱导的关节炎关节的pOCs中被观察到。腺病毒介导的fak相关非激酶在原始细胞中的表达以显性阴性方式抑制VEGF的作用。此外，关节内注射fak相关的非激酶病毒抑制poc的募集和骨破坏。我们的研究结果表明VEGF-Flt-1-FAK通路可能参与炎症性疾病引起的关节破坏。
Vascular endothelial growth factor (VEGF) plays a crucial role in the pathogenesis of inflammatory joint disease, including angiogenesis and synovitis. Rheumatoid arthritis is a chronic inflammatory disease characterized by progressive synovitis and subsequent bone destruction mediated by osteoclasts (OCs). In this study, we investigate the effects of VEGF on OC precursor cells (pOCs) using Raw cells and adjuvant-induced arthritis in rats. OCs and pOCs in the arthritic joints express VEGF and VEGF receptor type I (Flt-1). Raw cells also express Flt-1, and VEGF treatment stimulated chemotaxis, cell proliferation, the association of Flt-1 with focal adhesion kinase (FAK), and the tyrosine phosphorylation of FAK in Raw cells. The tyrosine phosphorylation of FAK was also observed in pOCs in the arthritic joints of adjuvant-induced arthritis. Adenovirus-mediated expression of FAK-related nonkinase in Raw cells inhibited the effects of VEGF in a dominant negative manner. Furthermore, intra-articular injection of the FAK-related nonkinase virus suppressed the recruitment of pOCs and bone destruction. Our results suggest the possible involvement of the VEGF-Flt-1-FAK pathway in inflammatory disease-induced joint destruction.