Goto Norio, Okazaki Ken, Akasaki Yukio, Ishihara Kohei, Murakami Koji, Koyano Kiyoshi, Ayukawa Yasunori, Yasunami Noriyuki, Masuzaki Tomohiro, Nakashima Yasuharu
Department of Orthopaedic Surgery, Graduate School of Medical Sciences, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
Section of Implant and Rehabilitative Dentistry, Division of Oral Rehabilitation, Faculty of Dental Science, Kyushu University, 3-1-1 Maidashi, Higashi-ku, Fukuoka, 812-8582, Japan.
J Orthop Res. 2017 Nov;35(11):2465-2475. doi: 10.1002/jor.23562. Epub 2017 Apr 13.
Statins are cholesterol-lowering drugs that inhibit 3-hydroxy-3-methylglutaryl-coenzyme A (HMG-CoA) reductase, a rate-limiting enzyme of the mevalonate pathway. The anti-inflammatory effect of statins has been reported in recent years. The present study investigated therapeutic effects of the local administration of statin in osteoarthritis (OA). We assessed clinically used statins and selected fluvastatin for further experimentation, as it showed potent anabolic and anti-catabolic effects on human OA chondrocytes. To achieve controlled intra-articular administration of statin, we developed an intra-articular injectable statin using poly(lactic-co-glycolic acid) (PLGA) as a drug delivery system (DDS). The release profile of the statin was evaluated in vitro. Finally, therapeutic effects of fluvastatin-loaded PLGA microspheres (FLU-PLGA) were tested in a rabbit OA model. Rabbit knees were divided into four subgroups: group 1-A, PLGA-treated group; group 1-B, PLGA contralateral saline control group; group 2-A, FLU-PLGA-treated group; and group 2-B, FLU-PLGA contralateral saline control group. Histological analysis 5 weeks after intra-articular injection revealed that OARSI scores were lower in group 2-A. No significant differences in OARSI scores were observed between groups 1-A, 1-B, and 2-B. This study indicates that a single intra-articular injection of fluvastatin-loaded PLGA microspheres could be a novel therapeutic approach for treating patients with OA. © 2017 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 35:2465-2475, 2017.
他汀类药物是一类降胆固醇药物，可抑制3-羟基-3-甲基戊二酰辅酶A（HMG-CoA）还原酶，这是甲羟戊酸途径的限速酶。近年来，已有报道称他汀类药物具有抗炎作用。本研究调查了局部应用他汀类药物治疗骨关节炎（OA）的效果。我们评估了临床使用的他汀类药物，并选择氟伐他汀进行进一步实验，因为它对人OA软骨细胞显示出强大的合成代谢和抗分解代谢作用。为了实现他汀类药物的关节内可控给药，我们开发了一种以聚乳酸-乙醇酸共聚物（PLGA）作为药物递送系统（DDS）的关节内注射用他汀类药物。在体外评估了他汀类药物的释放曲线。最后，在兔OA模型中测试了载氟伐他汀PLGA微球（FLU-PLGA）的治疗效果。兔膝关节分为四个亚组：1-A组，PLGA治疗组；1-B组，PLGA对侧生理盐水对照组；2-A组，FLU-PLGA治疗组；2-B组，FLU-PLGA对侧生理盐水对照组。关节内注射5周后的组织学分析显示，2-A组的骨关节炎研究学会（OARSI）评分较低。在1-A组、1-B组和2-B组之间，未观察到OARSI评分有显著差异。本研究表明，单次关节内注射载氟伐他汀PLGA微球可能是治疗OA患者的一种新的治疗方法。©2017骨科学研究学会。由威利期刊公司出版。《矫形外科学研究》35:2465 - 2475，2017年。
