Fitzgerald J, Rich C, Burkhardt D, Allen J, Herzka A S, Little C B
Oregon Health and Science University, Department of Orthopaedics and Rehabilitation, Portland, OR 97239, USA.
Osteoarthritis Cartilage. 2008 Nov;16(11):1319-26. doi: 10.1016/j.joca.2008.03.014. Epub 2008 May 1.
A major clinical problem in Orthopaedics is the repair of traumatic articular cartilage lesions. The MRL/MpJ strain of mice has the remarkable ability to regenerate ear hole punch wounds seamlessly including the scarless replacement of multiple tissues. The objective of this study was to assess whether articular cartilage defects repair or regenerate in the MRL/MpJ 'healer' strain of mice.
Full thickness and partial thickness lesions were introduced into trochlear groove articular cartilage of MRL/MpJ and C57Bl/6 mice, a control strain that does not undergo ear hole regeneration. The wound sites were assessed 6 weeks and 12 weeks post-surgery using a histological scoring scheme and immunohistochemistry for markers of articular cartilage including proteoglycan, collagen II and collagen VI.
The partial thickness lesions did not repair in either strain. However, at both 6 weeks and 12 weeks timepoints the MRL/MpJ mice had a superior healing response of full thickness lesions with abundant chondrocytes and an extracellular matrix rich in proteoglycan, collagen II and collagen VI at the wound site. At the 12 week timepoint the enhanced cartilage healing was restricted to male MRL/MpJ mice. In contrast, the C57Bl/6 control strain produced an extracellular matrix at the wound site that, overall, had significantly less matrix proteoglycan and collagen II.
Male MRL/MpJ mice appear to possess an intrinsic ability to 'regenerate' articular cartilage. Understanding the biochemical and genetic basis for articular cartilage regeneration may open up new treatment options for traumatic articular cartilage defects.
骨科领域的一个主要临床问题是创伤性关节软骨损伤的修复。MRL/MpJ品系小鼠具有非凡的能力,能够无缝再生耳洞穿刺伤口,包括多种组织的无瘢痕替代。本研究的目的是评估MRL/MpJ“愈合型”品系小鼠的关节软骨缺损能否修复或再生。
在MRL/MpJ小鼠和C57Bl/6小鼠(一种不能进行耳洞再生的对照品系)的滑车沟关节软骨上制造全层和部分厚度的损伤。术后6周和12周,使用组织学评分方案和免疫组织化学方法评估伤口部位,检测关节软骨标志物,包括蛋白聚糖、胶原蛋白II和胶原蛋白VI。
两种品系的部分厚度损伤均未修复。然而,在6周和12周的时间点,MRL/MpJ小鼠对全层损伤具有更好的愈合反应,伤口部位有丰富的软骨细胞以及富含蛋白聚糖、胶原蛋白II和胶原蛋白VI的细胞外基质。在12周时间点,软骨愈合增强仅限于雄性MRL/MpJ小鼠。相比之下,C57Bl/6对照品系在伤口部位产生的细胞外基质总体上基质蛋白聚糖和胶原蛋白II明显较少。
雄性MRL/MpJ小鼠似乎具有“再生”关节软骨的内在能力。了解关节软骨再生的生化和遗传基础可能为创伤性关节软骨缺损开辟新的治疗选择。