日本研究人员9日报告说，他们最新研究发现一种名为“Id4”的蛋白质对于骨骼的形成具有重要作用。
埼玉大学冈崎康司领导的研究小组在9日出版的美国《科学公共图书馆遗传卷》上发表论文介绍说，骨髓干细胞会分化为制造骨骼的成骨细胞和脂肪细胞，但是骨质疏松症患者的干细胞分化偏向于脂肪细胞，从而导致骨骼变脆弱。
研究小组将老鼠的干细胞分别分化为成骨细胞和脂肪细胞。分析发现，“Id4”蛋白质能够促进骨髓干细胞向成骨细胞的分化，而遏制向脂肪细胞的分化。进一步研究发现，这是因为“Id4”蛋白质会间接激活一种名为“Runx2”的促进骨骼形成的蛋白质。
在随后的实验中，研究人员通过基因工程技术，培育出不含编码“Id4”蛋白质的基因的老鼠。结果发现与正常老鼠相比，这种老鼠的骨量减少了约60％，骨髓内的脂肪细胞却非常多。
>>>借着上海世博会的良好契机，"第一届肿瘤基础和转化医学国际研讨会"将于2010年10月12日在中国上海盛大开幕，这将为广大活跃在肿瘤基础和转化医学第一线的科研工作者提供一个互动交流的平台。
会议官方网站：www.cancerasia.org
冈崎康司认为，将来科研人员如果能够发现激活“Id4”蛋白质的物质，就有可能开发出治疗骨质疏松症的新药。(生物谷Bioon.net)
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Nature Medicine：破解促进骨损害的分子机制
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英国最新发现将有助于治疗骨质疏松
生物谷推荐原文出处：
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
