Background:Microfracture is one surgical treatment strategy for osteochondral lesions of the talus (OLTs) but results in fibrocartilage repair tissue, which has inferior mechanical properties to native hyaline cartilage. Biological regulation of microfracture has been suggested to improve the quality of cartilage repair in patients.Purpose:To determine if administration of losartan, fisetin, or losartan and fisetin combined can enhance microfracture-mediated cartilage repair of OLTs in a rabbit model.Study Design:Controlled laboratory study.Methods:Four-month-old female rabbits were divided into the following groups (8 rabbits per group): microfracture only (microfracture), microfracture plus losartan (losartan), microfracture plus fisetin (fisetin), and microfracture plus losartan and fisetin (losartan+fisetin). A 2.7-mm osteochondral defect and 4 microfracture holes were created in the talar dome cartilage. The rabbits were administered losartan (10 mg/kg/day), fisetin (20 mg/kg/day), or losartan and fisetin orally until euthanized 12 weeks after surgery. Gross evaluation, micro–computed tomography, histology, and immunohistochemistry evaluations of the osteochondral defects were performed as well as quantitative polymerase chain reaction of capsule tissue and enzyme-linked immunosorbent assay of serum.Results:The losartan and fisetin groups had increased International Cartilage Regeneration & Joint Preservation Society macroscopic scores with improved cartilage repair and enhanced subchondral bone healing compared with the microfracture group. However, the losartan+fisetin group did not show a synergistic effect. O’Driscoll histology scores were higher in the losartan and fisetin groups compared with the microfracture group, while the losartan+fisetin group had a lower score than the losartan, fisetin, and microfracture groups. Collagen type 2 staining revealed organized chondrocytes in the losartan and fisetin groups, but the losartan+fisetin group did not show improvement when compared with other groups. Fisetin treatment decreased catalase and transforming growth factor-β1–activated kinase 1 expression in capsular tissue.Conclusion:Concomitant microfracture and biological regulation, using oral administration of either losartan or fisetin, may improve cartilage healing of OLTs; however, losartan and fisetin combined in the current drug administration regimen does not appear to provide synergistic effects.Clinical Relevance:Oral intake of losartan or fisetin may result in beneficial effects on microfracture-mediated cartilage repair of OLTs.

中文翻译：

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氯沙坦和非瑟酮对兔模型微骨折介导的踝关节软骨修复的影响


背景： 微骨折是距骨软骨病变 （OLTs） 的一种手术治疗策略，但导致纤维软骨修复组织，其机械性能不如天然透明软骨。微骨折的生物调节被认为可以提高患者软骨修复的质量。目的： 确定氯沙坦、非瑟酮或氯沙坦和非瑟酮联合给药是否可以增强兔模型中微骨折介导的 OLTs 软骨修复。研究设计： 对照实验室研究。方法：将 4 月龄雌性兔子分为以下组 （每组 8 只兔子）：仅微骨折组 （microfracture）、微骨折加氯沙坦 （losartan） 、微骨折加非瑟酮 （fisetin） 和微骨折加氯沙坦和非瑟酮 （losartan + fisetin）。在距骨圆顶软骨上创建了一个 2.7 mm 的骨软骨缺损和 4 个微骨折孔。兔子口服氯沙坦 （10 mg/kg/天）、非瑟酮 （20 mg/kg/天） 或口服氯沙坦和非瑟酮，直至术后 12 周安乐死。对骨软骨缺损进行大体评估、显微计算机断层扫描、组织学和免疫组化评估，以及胶囊组织的定量聚合酶链反应和血清的酶联免疫吸附测定。结果： 与微骨折组相比，氯沙坦和非瑟酮组在国际软骨再生与关节保护协会的宏观评分中有所提高，软骨修复得到改善，软骨下骨愈合得到增强。然而，氯沙坦 + 非瑟酮组未显示出协同作用。 与微骨折组相比，氯沙坦和非瑟酮组的 O'Driscoll 组织学评分较高，而氯沙坦 + 非瑟酮组的评分低于氯沙坦、非瑟酮和微骨折组。2 型胶原染色显示氯沙坦和非瑟酮组有组织的软骨细胞，但氯沙坦 + 非瑟酮组与其他组相比未表现出改善。非瑟酮处理降低了囊组织中过氧化氢酶和转化生长因子-β1 激活激酶 1 的表达。结论： 口服氯沙坦或非瑟酮伴随微骨折和生物调节，可改善 OLTs 的软骨愈合;然而，在目前的药物给药方案中，氯沙坦和非瑟酮联合使用似乎没有提供协同作用。临床相关性： 口服氯沙坦或非瑟酮可能对微骨折介导的 OLTs 软骨修复产生有益影响。