日本科學(xué)家在最新一期《自然·遺傳學(xué)》雜志網(wǎng)絡(luò)版上發(fā)表報(bào)告說,，他們發(fā)現(xiàn)了對肘關(guān)節(jié)和膝關(guān)節(jié)發(fā)育起關(guān)鍵作用的一種蛋白質(zhì)。
日本理化研究所16日發(fā)表新聞公報(bào)說,，該機(jī)構(gòu)科學(xué)家發(fā)現(xiàn),，一種名為纖維母細(xì)胞生長因子9（FGF9）的蛋白質(zhì)具有特殊作用。FGF9一般被認(rèn)為與軟骨和骨形成相關(guān),，但具體作用一直不大清楚,。理化研究所科學(xué)家對實(shí)驗(yàn)鼠進(jìn)行研究后發(fā)現(xiàn)，當(dāng)FGF9的氨基酸序列發(fā)生變異時(shí),，會(huì)導(dǎo)致出現(xiàn)肘關(guān)節(jié)和膝關(guān)節(jié)閉合的情況,，進(jìn)而造成實(shí)驗(yàn)鼠肘關(guān)節(jié)和膝關(guān)節(jié)骨骼異常，步行困難,。
進(jìn)一步研究發(fā)現(xiàn),，這是因?yàn)樽儺惖腇GF9在傳遞信息時(shí)發(fā)生了錯(cuò)誤，導(dǎo)致肘關(guān)節(jié)和膝關(guān)節(jié)閉合,。這說明,，F(xiàn)GF9對肘關(guān)節(jié)和膝關(guān)節(jié)生長發(fā)育有影響。研究人員還發(fā)現(xiàn),，正常的FGF9在身體內(nèi)發(fā)生名為“二聚化”的反應(yīng)后,，經(jīng)過與硫酸肝素糖蛋白結(jié)合，可確定肘關(guān)節(jié)和膝關(guān)節(jié)組織內(nèi)FGF9的信息所要到達(dá)的正確部位,，從而引導(dǎo)肘關(guān)節(jié)和膝關(guān)節(jié)正常發(fā)育,。
公報(bào)說，新研究成果有望用于開發(fā)在身體組織內(nèi)滲透性良好的關(guān)節(jié)炎治療藥物,。（生物谷Bioon.com）
生物谷推薦原始出處：
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.
