N-Acylethanolamine acid amidase (NAAA) inhibitor F215 as a novel therapeutic agent for osteoarthritis
N-Acylethanolamine acid amidase (NAAA) inhibitor F215 as a novel therapeutic agent for osteoarthritis
复制标题
N-酰基乙醇胺酰胺酶 (NAAA) 抑制剂 F215 作为骨关节炎的新型治疗剂
DOI：
10.1016/j.phrs.2019.104264
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发表时间：
2019-07-01
影响因子：
9.3
通讯作者：
Li, Yuhang
中科院分区：
文献类型：
--
作者：
Zhou, Pan;Xiang, Lei;Li, Yuhang
骨关节炎（OA）以软骨损伤、滑膜炎炎症和慢性疼痛为特征，是一种常见的退行性关节疾病，可能导致身体残疾。在本研究中，我们首先探讨了 N-酰基乙醇胺酰胺酶 (NAAA) 与 OA 进展之间的关联，然后检查了 NAAA 抑制剂 F215 减轻骨关节炎的能力。在 MIA 诱导的骨关节炎大鼠中，滑膜和腰脊髓中 NAAA 表达增加，PEA 水平降低。 F215（i.a. 和 i.p.）通过直接增加关节中的 PEA 水平或使 PEA 水平正常化并消除脊髓中的炎症，显着防止软骨损伤和滑膜炎症。此外，F215还显着减轻了大鼠的骨关节炎疼痛，并且F215的治疗作用被PPAR-a拮抗剂MK886阻断。结果显示，NAAA 可能与 OA 进展有关，NAAA 抑制剂 F215 治疗可通过预防软骨损伤、减少炎症和减轻疼痛来缓解 OA 发展。我们的研究表明 NAAA 抑制剂可能是治疗 OA 的新型治疗剂。
Osteoarthritis (OA), characterized by cartilage damage, synovitis inflammation and chronic pain, is a common degenerative joint disease that may lead to physical disability. In the present study, we first explored the association between N-Acylethanolamine acid amidase (NAAA) and OA progression, and then examined the capability of the NAAA inhibitor F215 to attenuate osteoarthritis. Increased NAAA expressions and decreased PEA levels in synovial membrane and lumbar spinal cord were observed in MIA induced osteoarthritic rats. F215 (i.a., and i.p.) significantly protected against cartilage damage and synovial inflammation by directly increasing PEA levels in joints, or normalization of PEA levels and resolution of inflammation in spinal cord. Moreover, F215 also markedly alleviated osteoarthritic pain in rats, and the therapeutic effects of F215 were blocked by the PPAR-a antagonist MK886. The results revealed that NAAA may has been implicated in OA progression, and treatment with NAAA inhibitor F215 alleviated OA development by preventing cartilage damage, reducing inflammation, and alleviating pain. Our study suggested that NAAA inhibitor might be a novel therapeutic agent for OA treatment.