日本研究人員9日報告說，他們最新研究發(fā)現(xiàn)一種名為“Id4”的蛋白質(zhì)對于骨骼的形成具有重要作用。
埼玉大學岡崎康司領導的研究小組在9日出版的美國《科學公共圖書館遺傳卷》上發(fā)表論文介紹說,，骨髓干細胞會分化為制造骨骼的成骨細胞和脂肪細胞，但是骨質(zhì)疏松癥患者的干細胞分化偏向于脂肪細胞,，從而導致骨骼變脆弱,。
研究小組將老鼠的干細胞分別分化為成骨細胞和脂肪細胞。分析發(fā)現(xiàn),，“Id4”蛋白質(zhì)能夠促進骨髓干細胞向成骨細胞的分化,，而遏制向脂肪細胞的分化。進一步研究發(fā)現(xiàn)，這是因為“Id4”蛋白質(zhì)會間接激活一種名為“Runx2”的促進骨骼形成的蛋白質(zhì),。
在隨后的實驗中,，研究人員通過基因工程技術，培育出不含編碼“Id4”蛋白質(zhì)的基因的老鼠,。結(jié)果發(fā)現(xiàn)與正常老鼠相比,，這種老鼠的骨量減少了約60％，骨髓內(nèi)的脂肪細胞卻非常多,。
>>>借著上海世博會的良好契機，"第一屆腫瘤基礎和轉(zhuǎn)化醫(yī)學國際研討會"將于2010年10月12日在中國上海盛大開幕,，這將為廣大活躍在腫瘤基礎和轉(zhuǎn)化醫(yī)學第一線的科研工作者提供一個互動交流的平臺,。
會議官方網(wǎng)站：www.cancerasia.org
岡崎康司認為，將來科研人員如果能夠發(fā)現(xiàn)激活“Id4”蛋白質(zhì)的物質(zhì),，就有可能開發(fā)出治療骨質(zhì)疏松癥的新藥,。(生物谷Bioon.net)
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生物谷推薦原文出處：
PLoS Genetics doi:10.1371/journal.pgen.1001019
Id4, a New Candidate Gene for Senile Osteoporosis, Acts as a Molecular Switch Promoting Osteoblast Differentiation
Yoshimi Tokuzawa1#, Ken Yagi1#, Yzumi Yamashita1, Yutaka Nakachi1, Itoshi Nikaido1, Hidemasa Bono1, Yuichi Ninomiya1, Yukiko Kanesaki-Yatsuka1, Masumi Akita2, Hiromi Motegi3, Shigeharu Wakana3, Tetsuo Noda3,4, Fred Sablitzky5, Shigeki Arai6, Riki Kurokawa6, Toru Fukuda7, Takenobu Katagiri7, Christian Sch?nbach8,9, Tatsuo Suda1, Yosuke Mizuno1, Yasushi Okazaki1*
Excessive accumulation of bone marrow adipocytes observed in senile osteoporosis or age-related osteopenia is caused by the unbalanced differentiation of MSCs into bone marrow adipocytes or osteoblasts. Several transcription factors are known to regulate the balance between adipocyte and osteoblast differentiation. However, the molecular mechanisms that regulate the balance between adipocyte and osteoblast differentiation in the bone marrow have yet to be elucidated. To identify candidate genes associated with senile osteoporosis, we performed genome-wide expression analyses of differentiating osteoblasts and adipocytes. Among transcription factors that were enriched in the early phase of differentiation, Id4 was identified as a key molecule affecting the differentiation of both cell types. Experiments using bone marrow-derived stromal cell line ST2 and Id4-deficient mice showed that lack of Id4 drastically reduces osteoblast differentiation and drives differentiation toward adipocytes. On the other hand knockdown of Id4 in adipogenic-induced ST2 cells increased the expression of Pparγ2, a master regulator of adipocyte differentiation. Similar results were observed in bone marrow cells of femur and tibia of Id4-deficient mice. However the effect of Id4 on Pparγ2 and adipocyte differentiation is unlikely to be of direct nature. The mechanism of Id4 promoting osteoblast differentiation is associated with the Id4-mediated release of Hes1 from Hes1-Hey2 complexes. Hes1 increases the stability and transcriptional activity of Runx2, a key molecule of osteoblast differentiation, which results in an enhanced osteoblast-specific gene expression. The new role of Id4 in promoting osteoblast differentiation renders it a target for preventing the onset of senile osteoporosis.
1 Division of Functional Genomics and Systems Medicine, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Saitama, Japan, 2 Division of Morphological Science, Biomedical Research Center, Saitama Medical University, Iruma-gun, Saitama, Japan, 3 RIKEN BioResource Center, Tsukuba, Ibaraki, Japan, 4 The Cancer Institute of the Japanese Foundation for Cancer Research, Koto-ward, Tokyo, Japan, 5 Developmental Genetics and Gene Control, Institute of Genetics, University of Nottingham, Queen's Medical Center, Nottingham, United Kingdom, 6 Division of Gene Structure and Function, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Saitama, Japan, 7 Division of Pathophysiology, Research Center for Genomic Medicine, Saitama Medical University, Hidaka, Saitama, Japan, 8 Division of Genomics and Genetics, Nanyang Technological University School of Biological Sciences, Singapore, Singapore, 9 Department of Bioscience and Bioinformatics, Kyushu Institute of Technology, Iizuka, Fukuoka, Japan
