Malemud Charles J
Department of Medicine/Division of Rheumatic Diseases, Case Western Reserve University School of Medicine and University Hospitals of Cleveland, 2061 Cornell Road, Room 207 Cleveland, OH 44106-5076, USA.
Clin Chim Acta. 2007 Jan;375(1-2):10-9. doi: 10.1016/j.cca.2006.06.033. Epub 2006 Jul 3.
Adult rheumatoid arthritis (RA), a systemic autoimmune disorder of unknown etiology, is characterized by dysfunctional cellular and humoral immunity, enhanced migration and attachment of peripheral macrophages and pro-inflammatory leukocytes to the synovium and articular cartilage of diarthrodial joints. The progressive destruction of cartilage and bone in RA is a result of elevated pro-inflammatory cytokine gene expression, synovial neovascularization, proteinase-mediated dissolution of articular cartilage matrix and osteoclast-mediated subchondral bone resorption. Juvenile chronic arthritis (JCA) is disease with manifestations similar to adult RA that occurs in childhood. JCA usually causes precocious joint destruction and often also presents with evidence of growth plate anomalies and reduced stature. Three proteins play an integral role in both adult RA and JCA. These are somatotropin (also called pituitary growth hormone (GH)), vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). GH is responsible for regulating long bone growth and skeletal maturation through its capacity to stimulate insulin-like growth factor-I (IGF-1) synthesis by hepatocytes. Mechanisms responsible for growth plate disturbances and short stature in children with JCA include deficient GH production, GH-insensitivity resulting from defects in the GH receptor, suppressed IGF-1 synthesis or neutralization of IGF-1 action by IGF-1 binding proteins (IGFBPs). In addition, GH has also been implicated in perpetuating inflammation and pain in adult RA. VEGF has been shown to be the critical angiogenesis factor responsible for vascular proliferation and blood vessel invasion of the synovial lining membrane in RA. Acidic FGF (FGF-1) and basic FGF (FGF-2) have also been implicated in aberrant synoviocyte proliferation (i.e. synovial hyperplasia) and apoptosis resistance in adult RA.
成人类风湿性关节炎（RA）是一种病因不明的全身性自身免疫性疾病，其特征在于细胞免疫和体液免疫功能失调，外周巨噬细胞和促炎性白细胞向滑膜关节的滑膜和关节软骨的迁移和附着增强。RA中软骨和骨的进行性破坏是促炎性细胞因子基因表达升高、滑膜新生血管形成、蛋白酶介导的关节软骨基质溶解以及破骨细胞介导的软骨下骨吸收的结果。青少年慢性关节炎（JCA）是一种在儿童期发生的、临床表现与成人RA相似的疾病。JCA通常会导致关节过早破坏，并且常常还伴有生长板异常和身材矮小的迹象。三种蛋白质在成人RA和JCA中都起着不可或缺的作用。这些蛋白质是生长激素（也称为垂体生长激素（GH））、血管内皮生长因子（VEGF）和成纤维细胞生长因子（FGF）。GH通过刺激肝细胞合成胰岛素样生长因子-I（IGF-1）来调节长骨生长和骨骼成熟。导致JCA患儿生长板紊乱和身材矮小的机制包括GH分泌不足、GH受体缺陷导致的GH不敏感、IGF-1合成受抑或IGF-1结合蛋白（IGFBPs）对IGF-1作用的中和。此外，GH还与成人RA的炎症持续和疼痛有关。VEGF已被证明是RA中负责滑膜衬里膜血管增殖和血管侵袭的关键血管生成因子。酸性FGF（FGF-1）和碱性FGF（FGF-2）也与成人RA中滑膜细胞异常增殖（即滑膜增生）和抗凋亡有关。
