日本研究人员日前发现了一种对防止关节炎具有重要作用的小分子，有可能催生治疗关节炎和类风湿性关节炎的新方法。
日本国立儿童健康和发展研究所系统发生和再生医学研究部主任浅原弘嗣等研究人员注意到，人类和实验鼠的软骨细胞中富含“miR140”分子，这是一种微型核糖核酸，也即长约22个核苷酸的小分子非编码核糖核酸。研究人员通过基因操作，培育出几乎不含“miR140”分子的实验鼠，并人为使它们患上关节炎。结果，与普通实验鼠相比，不含“miR140”分子的实验鼠软骨的损伤程度要严重得多。反之，通过基因操作令实验鼠体内的“miR140”分子增加，那么在同样罹患关节炎的情况下，这些实验鼠软骨的状态则非常良好。
研究人员解释说，关节炎主要是构成软骨的蛋白质被称为“ADAMTS5”的酶分解造成的，“miR140”则可以抑制这种酶的活动。
研究还发现，体内几乎不含“c”分子的实验鼠，手脚和尾巴都会变短，这证明这种分子对动物骨骼的形成具有重要作用。
核糖核酸是遗传信息的载体，和蛋白质的生物合成有密切的关系，而微型核糖核酸并不参与蛋白质合成，一直被认为是“无用”的。但是此次研究成果表明，微型核糖核酸发挥着其他作用。
这一研究成果已刊登在最新一期美国《基因与发育》杂志上。
推荐原文出处：
Gene " Development doi:10.1101/gad.1915510
MicroRNA-140 plays dual roles in both cartilage development and homeostasis
Shigeru Miyaki1,4, Tempei Sato2,4, Atsushi Inoue2, Shuhei Otsuki1, Yoshiaki Ito2, Shigetoshi Yokoyama2, Yoshio Kato3, Fuko Takemoto2, Tomoyuki Nakasa2, Satoshi Yamashita2, Shuji Takada2, Martin K. Lotz1, Hiroe Ueno-Kudo2 and Hiroshi Asahara1,2,5
Osteoarthritis (OA), the most prevalent aging-related joint disease, is characterized by insufficient extracellular matrix synthesis and articular cartilage degradation, mediated by several proteinases, including Adamts-5. miR-140 is one of a very limited number of noncoding microRNAs (miRNAs) specifically expressed in cartilage; however, its role in development and/or tissue maintenance is largely uncharacterized. To examine miR-140 function in tissue development and homeostasis, we generated a mouse line through a targeted deletion of miR-140. miR-140?/? mice manifested a mild skeletal phenotype with a short stature, although the structure of the articular joint cartilage appeared grossly normal in 1-mo-old miR-140?/? mice. Interestingly, miR-140?/? mice showed age-related OA-like changes characterized by proteoglycan loss and fibrillation of articular cartilage. Conversely, transgenic (TG) mice overexpressing miR-140 in cartilage were resistant to antigen-induced arthritis. OA-like changes in miR-140-deficient mice can be attributed, in part, to elevated Adamts-5 expression, regulated directly by miR-140. We show that miR-140 regulates cartilage development and homeostasis, and its loss contributes to the development of age-related OA-like changes.
