Roman-Blas J A, Jimenez S A
Division of Rheumatology, Department of Medicine, Thomas Jefferson University, Philadelphia, PA19107-5541, USA.
Osteoarthritis Cartilage. 2006 Sep;14(9):839-48. doi: 10.1016/j.joca.2006.04.008. Epub 2006 May 26.
The family of nuclear factor-kappaB (NF-kappaB) transcription factors is intimately involved in the regulation of expression of numerous genes in the setting of the inflammatory response. Since inflammatory processes play a fundamental role in the damage of articular tissues, many in vitro and in vivo studies have examined the contribution of components of the NF-kappaB signaling pathways to the pathogenesis of various rheumatic diseases, in particular, of osteoarthritis (OA) and rheumatoid arthritis (RA). Inflammation, cartilage degradation, cell proliferation, angiogenesis and pannus formation are processes in which the role of NF-kappaB is prominent. Consequently, large efforts have been devoted to the study of the pharmacologic modulation of the NF-kappaB pathways. These studies have employed currently available therapeutic agents including non-steroidal anti-inflammatory drugs, corticosteroids, nutraceuticals and disease-modifying anti-rheumatic drugs, as well as novel small molecule inhibitors targeted to specific proteins of the NF-kappaB pathways. In addition, promising strategies such as improved antisense DNA therapy and RNA interference have been examined with encouraging results. However, since NF-kappaB also plays a crucial beneficial role in normal physiology and technical problems for effective gene therapy still remain, further research will be needed before NF-kappaB-aimed strategies become an effective therapy for joint diseases, such as OA and RA.
核因子-κB（NF-κB）转录因子家族密切参与炎症反应中众多基因表达的调控。由于炎症过程在关节组织损伤中起重要作用，许多体外和体内研究都探讨了NF-κB信号通路的组成成分在各种风湿性疾病，特别是骨关节炎（OA）和类风湿关节炎（RA）发病机制中的作用。炎症、软骨降解、细胞增殖、血管生成和血管翳形成是NF-κB发挥突出作用的过程。因此，人们在研究NF-κB通路的药理调节方面付出了巨大努力。这些研究使用了目前可用的治疗药物，包括非甾体抗炎药、皮质类固醇、营养保健品和改善病情的抗风湿药物，以及针对NF-κB通路特定蛋白的新型小分子抑制剂。此外，诸如改进的反义DNA疗法和RNA干扰等有前景的策略也已得到研究，结果令人鼓舞。然而，由于NF-κB在正常生理中也起着至关重要的有益作用，并且有效基因治疗的技术问题仍然存在，在以NF-κB为靶点的策略成为OA和RA等关节疾病的有效治疗方法之前，还需要进一步研究。
