BACKGROUND Microfracture or bone marrow stimulation (BMS) is often the first choice for clinical treatment of cartilage injuries; however, fibrocartilage, not pure hyaline cartilage, has been reported because of the development of fibrosis in the repair tissue. Transforming growth factor β1 (TGF-β1), which can promote fibrosis, can be inhibited by losartan and potentially be used to reduce fibrocartilage. HYPOTHESIS Blocking TGF-β1 would improve cartilage healing in a rabbit knee BMS model via decreasing the amount of fibrocartilage and increasing hyaline-like cartilage formation. STUDY DESIGN Controlled laboratory study. METHODS An osteochondral defect was made in the patellar groove of 48 New Zealand White rabbits. The rabbits were divided into 3 groups: a defect group (defect only), a BMS group (osteochondral defect + BMS), and a BMS + losartan group (osteochondral defect + BMS + losartan). For the rabbits in the BMS + losartan group, losartan was administrated orally from the day after surgery through the day of euthanasia. Rabbits were sacrificed 6 or 12 weeks postoperatively. Macroscopic appearance, microcomputed tomography, histological assessment, and TGF-β1 signaling pathway were evaluated at 6 and 12 weeks postoperatively. RESULTS The macroscopic assessment of the repair revealed that the BMS + losartan group was superior to the other groups tested. Microcomputed tomography showed superior healing of the bony defect in the BMS + losartan group in comparison with the other groups. Histologically, fibrosis in the repair tissue of the BMS + losartan group was significantly reduced when compared with the other groups. Results obtained with the modified O'Driscoll International Cartilage Repair Society grading system yielded significantly superior scores in the BMS + losartan group as compared with both the defect group and the BMS group (F value: 15.8, P < .001, P = .012, respectively). TGF-β1 signaling and TGF-β-activated kinase 1 of the BMS + losartan group were significantly suppressed in the synovial tissues. CONCLUSION By blocking TGF-β1 with losartan, the repair cartilage tissue after BMS was superior to the other groups and consisted primarily of hyaline cartilage. These results should be easily translated to the clinic because losartan is a Food and Drug Administration-approved drug and it can be combined with the BMS technique for optimal repair of chondral defects. CLINICAL RELEVANCE Biologically regulated marrow stimulation by blocking TGF-β1 (oral intake of losartan) provides superior repair via decreasing fibrocartilage formation and resulting in hyaline-like cartilage as compared with outcomes from BMS only.

中文翻译：

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氯沙坦口服给药通过阻断TGF-β1的生物学调控骨髓刺激可导致透明质酸样软骨修复：兔软骨软骨缺损模型。

背景技术微骨折或骨髓刺激（BMS）通常是临床治疗软骨损伤的首选方法。然而，由于修复组织中纤维化的发展，已经报道了纤维软骨而不是单纯的透明软骨。可以促进纤维化的转化生长因子β1（TGF-β1）可以被氯沙坦抑制，并有可能被用于减少纤维软骨。假设阻断TGF-β1可以通过减少纤维软骨的数量和增加透明质素样软骨的形成来改善兔膝BMS模型中的软骨愈合。研究设计受控的实验室研究。方法在48只新西兰白兔的pa骨沟中形成骨软骨缺损。将兔子分成3组：缺陷组（仅缺陷），BMS组（软骨软骨缺损+ BMS），和一个BMS +氯沙坦组（软骨缺损+ BMS +氯沙坦）。对于BMS +氯沙坦组的兔子，从手术后第二天至安乐死当天口服口服洛沙坦。术后6或12周处死兔子。在术后6周和12周对宏观外观，显微计算机断层扫描，组织学评估和TGF-β1信号通路进行评估。结果修复的宏观评估表明，BMS +氯沙坦组优于其他测试组。与其他组相比，微计算机断层扫描显示BMS +氯沙坦组的骨缺损具有良好的愈合。在组织学上，与其他组相比，BMS +氯沙坦组修复组织中的纤维化明显减少。用修饰的O'获得的结果 与缺陷组和BMS组相比，Driscoll国际软骨修复协会评分系统在BMS +氯沙坦组中的得分明显更高（F值分别为15.8，P <.001，P = .012）。在滑膜组织中，BMS +氯沙坦组的TGF-β1信号转导和TGF-β激活的激酶1被显着抑制。结论通过用氯沙坦阻断TGF-β1，BMS后的修复软骨组织优于其他组，主要由透明软骨组成。由于洛沙坦是美国食品药品监督管理局（FDA）批准的药物，可以将其结果轻松地应用于临床，并且可以将其与BMS技术结合使用，以最佳地修复软骨缺损。