Department of Zoology, University of Cambridge, Cambridge, United Kingdom.
Charles River Laboratories, Wilmington, Massachusetts, United States.
Elife. 2020 May 12;9:e53414. doi: 10.7554/eLife.53414.
Mammalian articular cartilage is an avascular tissue with poor capacity for spontaneous repair. Here, we show that embryonic development of cartilage in the skate () mirrors that of mammals, with developing chondrocytes co-expressing genes encoding the transcription factors Sox5, Sox6 and Sox9. However, in skate, transcriptional features of developing cartilage persist into adulthood, both in peripheral chondrocytes and in cells of the fibrous perichondrium that ensheaths the skeleton. Using pulse-chase label retention experiments and multiplexed in situ hybridization, we identify a population of cycling + perichondral progenitor cells that generate new cartilage during adult growth, and we show that persistence of chondrogenesis in adult skates correlates with ability to spontaneously repair cartilage injuries. Skates therefore offer a unique model for adult chondrogenesis and cartilage repair and may serve as inspiration for novel cell-based therapies for skeletal pathologies, such as osteoarthritis.
哺乳动物的关节软骨是一种无血管组织,其自发修复能力较差。在这里,我们发现软骨在鳐鱼中的胚胎发育与哺乳动物的发育过程相似,发育中的软骨细胞共同表达编码转录因子 Sox5、Sox6 和 Sox9 的基因。然而,在鳐鱼中,发育中的软骨的转录特征在成年期仍然存在,无论是在外周软骨细胞还是在包裹骨骼的纤维性软骨膜细胞中都是如此。通过脉冲追踪标记保留实验和多重原位杂交,我们鉴定出一群处于细胞周期中的+软骨膜祖细胞,它们在成年生长过程中产生新的软骨,我们还表明,成年鳐鱼的软骨发生的持久性与自发修复软骨损伤的能力相关。因此,鳐鱼为成体软骨发生和软骨修复提供了一个独特的模型,并且可能为骨骼疾病(如骨关节炎)的新型基于细胞的治疗方法提供灵感。