Loeser Richard F, Erickson Elizabeth A, Long David L
Department of Internal Medicine, Section of Molecular Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157, USA.
Curr Opin Rheumatol. 2008 Sep;20(5):581-6. doi: 10.1097/BOR.0b013e3283090463.
The mitogen-activated protein (MAP) kinases are intracellular signaling proteins which play a central role in controlling the activity of pathways that regulate production and activity of multiple mediators of joint tissue destruction. The therapeutic potential of MAP kinase inhibition in osteoarthritis was reviewed.
Results from basic research studies support the role of MAP kinases as central mediators that regulate expression of proinflammatory cytokines and metalloproteinases but also as potential pain mediators as well. Cell culture and animal model studies suggest that inhibition of MAP kinases might slow progression of osteoarthritis but trials of MAP kinase inhibitors in humans with osteoarthritis have not yet been reported. Safety concerns of the currently available inhibitors have limited their initial use to trials in conditions considered more severe than osteoarthritis.
MAP kinase inhibition has the potential to slow disease progression in osteoarthritis and also might reduce pain; however, safety concerns have limited the use of general MAP kinase inhibitors in humans. Further understanding of the function of specific isoforms of the MAP kinases as well as upstream and downstream effectors may lead to the development of more specific inhibitors with less toxicity that could eventually be used as structure-modifying drugs for osteoarthritis.
丝裂原活化蛋白（MAP）激酶是细胞内信号蛋白，在控制调节关节组织破坏多种介质产生和活性的信号通路活性方面发挥核心作用。本文综述了MAP激酶抑制在骨关节炎中的治疗潜力。
基础研究结果支持MAP激酶作为核心介质的作用，其不仅调节促炎细胞因子和金属蛋白酶的表达，还可能是潜在的疼痛介质。细胞培养和动物模型研究表明，抑制MAP激酶可能减缓骨关节炎的进展，但尚未有MAP激酶抑制剂在骨关节炎患者中的试验报道。目前可用抑制剂的安全性问题限制了其最初仅用于比骨关节炎更严重疾病的试验。
MAP激酶抑制有可能减缓骨关节炎的疾病进展，也可能减轻疼痛；然而，安全性问题限制了通用MAP激酶抑制剂在人类中的使用。进一步了解MAP激酶特定亚型以及上游和下游效应器的功能，可能会开发出毒性更小的更特异性抑制剂，最终可作为骨关节炎的结构修饰药物。
