Analysis and clinical application of new function of osteoprotegerin as anti-aging factor
| Project/Area Number |
17K19776
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| Research Category |
Grant-in-Aid for Challenging Research (Exploratory)
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| Allocation Type | Multi-year Fund |
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| Research Field |
Oral Science and related fields
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| Research Institution | Matsumoto Dental University |
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Principal Investigator |
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| Co-Investigator(Kenkyū-buntansha) |
小出 雅則 松本歯科大学, 総合歯科医学研究所, 准教授 (10367617)
吉成 伸夫 松本歯科大学, 歯学部, 教授 (20231699)
中本 哲自 朝日大学, 歯学部, 教授 (30514989)
中村 美どり 松本歯科大学, 歯学部, 准教授 (90278177)
上原 俊介 松本歯科大学, 歯学部, 講師 (90434480)
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| Project Period (FY) |
2017-06-30 – 2020-03-31
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| Project Status |
Completed (Fiscal Year 2019)
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| Budget Amount *help |
¥6,500,000 (Direct Cost: ¥5,000,000、Indirect Cost: ¥1,500,000)
Fiscal Year 2019: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2018: ¥1,560,000 (Direct Cost: ¥1,200,000、Indirect Cost: ¥360,000)
Fiscal Year 2017: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
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| Keywords | 骨代謝学 / 循環器学 / 骨粗鬆症 / 歯周病 / 抗加齢因子 / 骨カップリング / OPG / RANKL / 破骨細胞 / 骨芽細胞 / 骨代謝共役 / 心臓血管疾患 / 動脈硬化 / スクレロスチン / オステオプロテゲリン / 骨吸収 / 骨形成 / ＲＡＮＫＬ / ＯＰＧ / 心臓肥大 |
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| Outline of Final Research Achievements |
Osteoprotegerin (OPG) is expressed in cardiovascular system, and it may regulate not only bone metabolism but also contribute to the remodeling of heart and vasculature. We explored the roles of OPG in cardiovascular system using OPG-deficient mice. 1. OPG-deficient mice displayed the elevated systemic blood pressure, left ventricular hypertrophy with reduced contractility, compared with wild-type mice with age. Angiotensin II administration to the mice accelerated the heart failure. 2. Angiotensin II stimulation of OPG-deficient mice led to a high mortality due to aortic rupture. Histological analysis showed fragmentation of elastic fibers in the medial layer. We also analyzed the PCR arrays, and found the specific alteration of genes associated with extracellular matrix.
These results suggest that OPG may have protective roles to maintain the structural integrity against angiotensin II, and it may be a potential therapeutic target for heart failure and aortic dissection.
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| Academic Significance and Societal Importance of the Research Achievements |
本研究成果は、骨代謝学と循環器学（心臓血管学）の融合を目指したOsteocardiology(骨循環器学)の構築に寄与するに繋がる。OPG欠損マウスにおいて認められる骨粗鬆化、血管石灰化、心臓肥大といった形質の連関を探ることにより、抗加齢因子としてのOPGの新しい役割を証明することに成功した。OPGの抗加齢因子としての新しい機能として、歯周病や骨粗鬆症のみならず、心臓血管疾患、糖尿病、肥満といった全身疾患の治療のツールとして応用することの糸口を得ることが出来た。この研究結果は、骨代謝研究が各種生活習慣病の治療戦略に寄与する可能性を秘めており、今後の更なる研究の進展が期待される。
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Report
(4 results)
Research Products
(28 results)
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[Journal Article] Osteoprotegerin-dependent Mcell self-regulation balances gut infection and immunity.2020
Author(s)
Kimura S, Nakamura Y, Kobayashi N, Shiroguchi K, KawakamiE, Mutoh M, Takahashi-Iwanaga H, Yamada T, Hisamoto M, Nakamura M, Udagawa N, Sato S, KaishoT, Iwanaga T, Hase K.
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Journal Title
Nat Commun
Volume: 11
Issue: 1
Pages: 234-234
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Parathyroid Hormone Shifts Cell Fate of a Leptin Receptor-Marked Stromal Population from Adipogenic to Osteoblastic Lineage.2019
Author(s)
Yang M, Arai A, Udagawa N, Zhao L, Nishida D, Murakami K, Hiraga T, Takao-Kawabata R, Matsuo K, Komori T, Kobayashi Y, Takahashi N, Isogai Y, Ishizuya T, Yamaguchi A, Mizoguchi T
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Journal Title
J Bone Miner Res
Volume: 34
Issue: 10
Pages: 1952-1963
DOI
Related Report
Peer Reviewed / Open Access
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[Journal Article] Coupling of bone resorption and formation by RANKL reverse signalling.2018
Author(s)
Ikebuchi Y, Aoki S, Honma M, Hayashi M, Sugamori Y, Khan M, Kariya Y, Kato G, Tabata Y, Penninger JM, Udagawa N, Aoki K, Suzuki H
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Journal Title
Nature
Volume: 561
Issue: 7722
Pages: 195-200
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Protein kinase N3 promotes bone resorption by osteoclasts in response to Wnt5a-Ror2 signaling.2017
Author(s)
Uehara S, Udagawa N, Mukai H, Ishihara A, Maeda K, Yamashita T, Murakami K, Nishita M, Nakamura T, Kato S, Minami Y, Takahashi N and Kobayashi Y
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Journal Title
Sci Signal
Volume: 10
Issue: 494
DOI
Related Report
Peer Reviewed / Open Access
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[Presentation] Sialic acid-binding immunoglobulin-like lectin 15 (Siglec-15) plays important roles in the induction of both bone-resorbing activity of osteoclasts and osteoblast differentiation.2018
Author(s)
Udagawa N, Koide M, Uehara S, Arai A, Mizoguchi T, Yamashita T, Nakamura M, Kobayashi Y, Takahashi N, Kumakura S, Fukuda C, Tsuda E
Organizer
The American Society for Bone and Mineral Research (ASBMR) 2018 Annual Meeting
Related Report
Int'l Joint Research
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