Mitogen-activated protein kinases as therapeutic targets in osteoarthritis.
Mitogen-activated protein kinases as therapeutic targets in osteoarthritis.
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DOI：
10.1097/bor.0b013e3283090463
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发表时间：
2008-09
影响因子：
5.1
通讯作者：
Long DL
中科院分区：
文献类型：
--
作者：
Loeser RF;Erickson EA;Long DL
丝裂原激活蛋白 (MAP) 激酶是细胞内信号蛋白，在控制调节关节组织破坏的多种介质的产生和活性的途径的活性方面发挥着核心作用。综述了 MAP 激酶抑制在骨关节炎中的治疗潜力。基础研究的结果支持 MAP 激酶作为调节促炎细胞因子和金属蛋白酶表达的中心介质的作用，同时也作为潜在的疼痛介质。细胞培养和动物模型研究表明，抑制 MAP 激酶可能会减缓骨关节炎的进展，但尚未报道 MAP 激酶抑制剂在人类骨关节炎患者中的试验。目前可用的抑制剂的安全性问题限制了它们最初的使用，只能在比 OA 更严重的条件下进行试验。 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，安全性问题限制了一般 MAP 激酶抑制剂在人类中的使用。进一步了解 MAP 激酶特定异构体以及上游和下游效应子的功能可能会导致开发出毒性更小的更特异性抑制剂，最终可用作 OA 的结构修饰药物。
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 pro-inflammatory 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 OA. 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 OA.