日本科学家在最新一期《自然·遗传学》杂志网络版上发表报告说，他们发现了对肘关节和膝关节发育起关键作用的一种蛋白质。

日本理化研究所16日发表新闻公报说，该机构科学家发现，一种名为纤维母细胞生长因子9（FGF9）的蛋白质具有特殊作用。FGF9一般被认为与软骨和骨形成相关，但具体作用一直不大清楚。理化研究所科学家对实验鼠进行研究后发现，当FGF9的氨基酸序列发生变异时，会导致出现肘关节和膝关节闭合的情况，进而造成实验鼠肘关节和膝关节骨骼异常，步行困难。

进一步研究发现，这是因为变异的FGF9在传递信息时发生了错误，导致肘关节和膝关节闭合。这说明，FGF9对肘关节和膝关节生长发育有影响。研究人员还发现，正常的FGF9在身体内发生名为“二聚化”的反应后，经过与硫酸肝素糖蛋白结合，可确定肘关节和膝关节组织内FGF9的信息所要到达的正确部位，从而引导肘关节和膝关节正常发育。

公报说，新研究成果有望用于开发在身体组织内渗透性良好的关节炎治疗药物。

推荐原始出处：

Nature Genetics (15 Feb 2009), doi: 10.1038/ng.316, Article

FGF9 monomerA–dimer equilibrium regulates extracellular matrix affinity and tissue diffusion

Masayo Harada, Hirotaka Murakami, Akihiko Okawa, Noriaki Okimoto, Shuichi Hiraoka, Taka Nakahara, Ryogo Akasaka, Yo-ichi Shiraishi, Noriyuki Futatsugi, Yoko Mizutani-Koseki, Atsushi Kuroiwa, Mikako Shirouzu, Shigeyuki Yokoyama, Makoto Taiji, Sachiko Iseki, David M Ornitz, Haruhiko Koseki

RIKEN Research Center for Allergy and Immunology, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama, Kanagawa 230-0045, Japan. [2] Department of Immunology and Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.

The spontaneous dominant mouse mutant, Elbow knee synostosis (Eks), shows elbow and knee joint synosotsis, and premature fusion of cranial sutures. Here we identify a missense mutation in the Fgf9 gene that is responsible for the Eks mutation. Through investigation of the pathogenic mechanisms of joint and suture synostosis in Eks mice, we identify a key molecular mechanism that regulates FGF9 signaling in developing tissues. We show that the Eks mutation prevents homodimerization of the FGF9 protein and that monomeric FGF9 binds to heparin with a lower affinity than dimeric FGF9. These biochemical defects result in increased diffusion of the altered FGF9 protein (FGF9(Eks)) through developing tissues, leading to ectopic FGF9 signaling and repression of joint and suture development. We propose a mechanism in which the range of FGF9 signaling in developing tissues is limited by its ability to homodimerize and its affinity for extracellular matrix heparan sulfate proteoglycans.