Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, School of Medicine, Xiamen University, Xiamen, 361102, China; Department of Ophthalmology, Xiang'an Hospital of Xiamen University, Xiamen, 361102, China.
Eye Institute of Xiamen University, Fujian Provincial Key Laboratory of Ophthalmology and Visual Science, School of Medicine, Xiamen University, Xiamen, 361102, China.
Pharmacol Res. 2019 Jul;145:104264. doi: 10.1016/j.phrs.2019.104264. Epub 2019 May 4.
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-α 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.
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-酰基乙醇胺酸酰胺酶（NAAA）与 OA 进展之间的关系，然后研究了 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，观察到滑膜膜和腰椎脊髓中 NAAA 表达增加和 PEA 水平降低。F215（关节内和腹腔内）通过直接增加关节中的 PEA 水平或使 PEA 水平正常化并减轻脊髓炎症，显著防止软骨损伤和滑膜炎。此外，F215 还显著缓解了大鼠的骨关节炎疼痛，并且 F215 的治疗效果被 PPAR-α拮抗剂 MK886 阻断。结果表明，NAAA 可能与 OA 进展有关，并且通过防止软骨损伤、减少炎症和缓解疼痛，用 NAAA 抑制剂 F215 治疗可减轻 OA 的发展。我们的研究表明，NAAA 抑制剂可能是治疗 OA 的一种新型治疗剂。
