Department of Orthopaedic Surgery, McKay Orthopaedic Research Laboratory, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
Department of Clinical Studies, New Bolton Center, University of Pennsylvania School of Veterinary Medicine, Philadelphia, Pennsylvania, USA.
J Orthop Res. 2022 Mar;40(3):553-564. doi: 10.1002/jor.25063. Epub 2021 May 12.
Posttraumatic osteoarthritis is a disabling condition impacting the mostly young and active population. In the present study, we investigated the impact of intra-articular sprifermin, a recombinant truncated fibroblast growth factor 18, on the outcome of microfracture treatment, a widely used surgical technique to enhance cartilage healing at the site of injury. For this study, we created a cartilage defect and performed microfracture treatment in fetlock joints of 18 horses, treated joints with one of three doses of sprifermin (10, 30, or 100 μg) or with saline, hyaluronan, and evaluated animals functional and structural outcomes over 24 weeks. For primary outcome measures, we performed histological evaluations and gene expression analysis of aggrecan, collagen types I and II, and cartilage oligomeric matrix protein in three regions of interest. As secondary outcome measures, we examined animals' lameness, performed arthroscopic, radiographic, and computed tomography (CT) scan imaging and gross morphology assessment. We detected the highest treatment benefit following 100 μg sprifermin treatment. The overall histological assessment showed an improvement in the kissing region, and the expression of constitutive genes showed a concentration-dependent enhancement, especially in the peri-lesion area. We detected a significant improvement in lameness scores, arthroscopic evaluations, radiography, and CT scans following sprifermin treatment when results from three dose-treatment groups were combined. Our results demonstrated, for the first time, an enhancement on microfracture outcomes following sprifermin treatment suggesting a cartilage regenerative role and a potential benefit of sprifermin treatment in early cartilage injuries.
创伤后骨关节炎是一种致残性疾病,主要影响年轻且活跃的人群。在本研究中,我们研究了关节内 sprifermin(一种重组的截短成纤维细胞生长因子 18)对微骨折治疗结果的影响,微骨折治疗是一种广泛用于增强损伤部位软骨愈合的手术技术。在这项研究中,我们在马的球节关节中创建了一个软骨缺陷并进行了微骨折治疗,用三种剂量的 sprifermin(10、30 或 100μg)之一或生理盐水、透明质酸治疗关节,并在 24 周内评估动物的功能和结构结果。作为主要结果测量,我们对三个感兴趣区域的聚集蛋白聚糖、I 型和 II 型胶原以及软骨寡聚基质蛋白进行了组织学评估和基因表达分析。作为次要结果测量,我们检查了动物的跛行情况,进行了关节镜、放射照相和计算机断层扫描(CT)扫描成像以及大体形态评估。我们发现 100μg sprifermin 治疗的效果最好。总体组织学评估显示亲吻区有改善,组成性基因的表达呈浓度依赖性增强,尤其是在病变周围区域。当合并三个剂量治疗组的结果时,我们检测到 sprifermin 治疗后跛行评分、关节镜评估、放射照相和 CT 扫描有显著改善。我们的结果首次表明,sprifermin 治疗后微骨折治疗效果增强,提示其具有软骨再生作用,可能对早期软骨损伤有益。