生物谷報道：日本科學(xué)家在最新一期英國《自然—醫(yī)學(xué)》雜志網(wǎng)絡(luò)版上發(fā)表論文說,，腦內(nèi)物質(zhì)神經(jīng)介素U可調(diào)節(jié)骨密度,。
神經(jīng)介素U作用于下丘腦和消化器官末梢神經(jīng)等處，一般認(rèn)為它負(fù)責(zé)調(diào)節(jié)食欲,，能應(yīng)用于減肥等方面,。東京醫(yī)科齒科大學(xué)副教授竹田秀等人選擇兩組實驗鼠進行對照研究，一組正常,，一組則通過特殊培養(yǎng)不能合成神經(jīng)介素U,，結(jié)果發(fā)現(xiàn)，后一組實驗鼠腰椎的骨密度比前一種高約24%,，而脛骨的骨密度高約29%,。
研究人員向后一組實驗鼠大腦注射神經(jīng)介素U，經(jīng)過一段時間,，這些實驗鼠腰椎的骨密度大幅降低,。竹田秀因此推測，如果能開發(fā)出阻止神經(jīng)介素U發(fā)揮作用的藥物,，或許就可使骨質(zhì)疏松癥患者骨密度增加,。（新華網(wǎng)）
原始出處:
Nature Medicine
Published online: 16 September 2007 | doi:10.1038/nm1640
Central control of bone remodeling by neuromedin U
Shingo Sato1, Reiko Hanada2, Ayako Kimura1, Tomomi Abe3, Takahiro Matsumoto4,5, Makiko Iwasaki1, Hiroyuki Inose1, Takanori Ida2, Michihiro Mieda3, Yasuhiro Takeuchi6, Seiji Fukumoto7, Toshiro Fujita7, Shigeaki Kato4,5, Kenji Kangawa8, Masayasu Kojima2, Ken-ichi Shinomiya1 & Shu Takeda1
Bone remodeling, the function affected in osteoporosis, the most common of bone diseases, comprises two phases: bone formation by matrix-producing osteoblasts1 and bone resorption by osteoclasts2. The demonstration that the anorexigenic hormone leptin3, 4, 5 inhibits bone formation through a hypothalamic relay6, 7 suggests that other molecules that affect energy metabolism in the hypothalamus could also modulate bone mass. Neuromedin U (NMU) is an anorexigenic neuropeptide that acts independently of leptin through poorly defined mechanisms8, 9. Here we show that Nmu-deficient (Nmu-/-) mice have high bone mass owing to an increase in bone formation; this is more prominent in male mice than female mice. Physiological and cell-based assays indicate that NMU acts in the central nervous system, rather than directly on bone cells, to regulate bone remodeling. Notably, leptin- or sympathetic nervous system–mediated inhibition of bone formation6, 7 was abolished in Nmu-/- mice, which show an altered bone expression of molecular clock genes (mediators of the inhibition of bone formation by leptin). Moreover, treatment of wild-type mice with a natural agonist for the NMU receptor decreased bone mass. Collectively, these results suggest that NMU may be the first central mediator of leptin-dependent regulation of bone mass identified to date. Given the existence of inhibitors and activators of NMU action10, our results may influence the treatment of diseases involving low bone mass, such as osteoporosis.
Department of Orthopaedic Surgery, Graduate School, 21st Century Center of Excellence Program, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8519, Japan.
Division of Molecular Genetics, Institute of Life Science, Kurume University, 1-1 Hyakunen-kohen, Kurume, Fukuoka 839-0842, Japan.
Department of Molecular Neuroscience, Tokyo Medical and Dental University 1-5-45 Yushima, Bunkyo-ku,, Tokyo 113-8519, Japan.
Institute of Molecular and Cellular Biosciences, University of Tokyo, 1-1-1 Yayoi, Bunkyo-kux, Tokyo 113-0032, Japan.
Exploratory Research for Advanced Technology, Japan Science and Technology Agency, 4-1-8 Honcho, Kawaguchi, Saitama 332-0012, Japan.
Toranomon Hospital Endocrine Center, 2-2-2 Toranomon, Minato-ku, Tokyo 105-8470, Japan.
Division of Nephrology and Endocrinology, Department of Internal Medicine, University of Tokyo Hospital, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655, Japan.
Department of Biochemistry, National Cardiovascular Center Research Institute, 5-7-1 Fujishiro-dai, Suita-shi, Osaka 565-8565, Japan.
Correspondence to: Shu Takeda1 e-mail: [email protected]
