Askary Amjad, Smeeton Joanna, Paul Sandeep, Schindler Simone, Braasch Ingo, Ellis Nicholas A, Postlethwait John, Miller Craig T, Crump J Gage
Department of Stem Cell Biology and Regenerative Medicine, Keck School of Medicine of University of Southern California, Los Angeles, United States.
Eli and Edythe Broad CIRM Center for Regenerative Medicine and Stem Cell Research, Keck School of Medicine of University of Southern California, Los Angeles, United States.
Elife. 2016 Jul 19;5:e16415. doi: 10.7554/eLife.16415.
Synovial joints are the lubricated connections between the bones of our body that are commonly affected in arthritis. It is assumed that synovial joints first evolved as vertebrates came to land, with ray-finned fishes lacking lubricated joints. Here, we examine the expression and function of a critical lubricating protein of mammalian synovial joints, Prg4/Lubricin, in diverse ray-finned fishes. We find that Prg4 homologs are specifically enriched at the jaw and pectoral fin joints of zebrafish, stickleback, and gar, with genetic deletion of the zebrafish prg4b gene resulting in the same age-related degeneration of joints as seen in lubricin-deficient mice and humans. Our data support lubricated synovial joints evolving much earlier than currently accepted, at least in the common ancestor of all bony vertebrates. Establishment of the first arthritis model in the highly regenerative zebrafish will offer unique opportunities to understand the aetiology and possible treatment of synovial joint disease.
滑膜关节是我们身体骨骼之间的润滑连接，在关节炎中通常会受到影响。据推测，滑膜关节最初是随着脊椎动物登陆而进化的，辐鳍鱼类缺乏润滑关节。在这里，我们研究了哺乳动物滑膜关节的一种关键润滑蛋白Prg4/润滑素在多种辐鳍鱼类中的表达和功能。我们发现Prg4同源物在斑马鱼、棘鱼和雀鳝的颌关节和胸鳍关节中特异性富集，斑马鱼prg4b基因的基因缺失导致与润滑素缺乏的小鼠和人类中所见相同的与年龄相关的关节退化。我们的数据支持润滑滑膜关节的进化比目前公认的要早得多，至少在所有硬骨脊椎动物的共同祖先中是这样。在具有高度再生能力的斑马鱼中建立第一个关节炎模型将为了解滑膜关节疾病的病因和可能的治疗方法提供独特的机会。
