Minimodeling - a novel manner of bone formation: Investigation of "minimodeling factors" from osteocytes
| Project/Area Number |
21K19585
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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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| Review Section |
Medium-sized Section 57:Oral science and related fields
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| Research Institution | Hokkaido University |
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Principal Investigator |
AMIZUKA Norio 北海道大学, 歯学研究院, 教授 (30242431)
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| Project Period (FY) |
2021-07-09 – 2023-03-31
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| Project Status |
Completed (Fiscal Year 2022)
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| Budget Amount *help |
¥6,370,000 (Direct Cost: ¥4,900,000、Indirect Cost: ¥1,470,000)
Fiscal Year 2022: ¥2,990,000 (Direct Cost: ¥2,300,000、Indirect Cost: ¥690,000)
Fiscal Year 2021: ¥3,380,000 (Direct Cost: ¥2,600,000、Indirect Cost: ¥780,000)
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| Keywords | ミニモデリング / 骨細胞 / 骨リモデリング / エルデカルシトール / スクレロスチン |
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| Outline of Research at the Start |
ミニモデリングは、骨リモデリングとは異なる様式で誘導される新規の骨形成様式として注目を浴びているが、その機序については不明な点が多い。そこで、本研究では、骨細胞ネットワークによるスクレロスチン抑制、および、骨周囲の血管内皮・周囲細胞群から骨芽細胞・骨細胞への作用（骨血管連関）の両側面から検索することで、ミニモデリングの発生メカニズム、特に、“ミニモデリングファクター”の候補因子を絞り上げてゆきたい。本研究でミニモデリングのメカニズムや誘導ファクターが解明されれば、将来の骨代謝研究・臨床において大きなターニングポイントとなると考えられる。
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| Outline of Final Research Achievements |
In this study, we have attempted to examine minimodeling-based bone formation in the epiphyses and metaphyses of the long bones of eldecalcitol (ELD)-administered ovariectomized (OVX) rats. ELD administration increased bone volume by minimodeling in OVX rats. The epiphyses, rather than metaphyses, of the ELD group showed significantly higher frequency of minimodeling-based bone formation. The epiphyseal trabeculae seem to receive the mechanical stress from the joint, when compared to metaphyseal trabeculae extended from the growth plate cartilage. The percentage of sclerostin-positive osteocytes was significantly reduced in the minimodeling-induced new bone in the epiphyses but not in the metaphyses of the ELD groups. Taken together, it seems likely that ELD could efficiently induce minimodeling-based bone formation in the epiphyseal trabeculae which would easily receive the mechanical stress from the joint.
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| Academic Significance and Societal Importance of the Research Achievements |
ミニモデリングは、骨リモデリングとは異なる様式で骨形成を誘導する。これまでに、抗スクレロスチン抗体がミニモデリングを誘導することが知られているが、本研究では、エルデカルシトールがメカニカルストレスのかかる部位においてスクレロスチン産生を有意に抑制して、ミニモデリングを誘導することから、ミニモデリング誘導因子としてメカニカルストレスが強く示唆された。今回の結果は、骨粗鬆症治療において、薬剤治療だけでなく運動療法も組み合わせることで効率的にミニモデリングを誘導し骨量増加につながる可能性が得られた。
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Report
(3 results)
Research Products
(24 results)
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[Journal Article] Tmem174, a regulator of phosphate transporter prevents hyperphosphatemia.2022
Author(s)
Sasaki S, Shiozaki Y, Hanazaki A, Koike M, Tanifuji K, Uga M, Kawahara K, Kaneko I, Hasegawa T, Amizuka N, Miyamoto KI, Nagamori S, Kanai Y, Segawa H.
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Journal Title
Scientific Reports
Volume: 12巻1号
Issue: 1
Pages: 6353-6353
DOI
Related Report
Peer Reviewed / Open Access / Int'l Joint Research
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[Journal Article] Bone biopsy findings in patients receiving long-term bisphosphonate therapy for glucocorticoid-induced osteoporosis.2022
Author(s)
Takahata M., Shimizu T., Yamada T., Yamada S., Yamamoto T., Hasegawa T., Fujita R., Kobayashi H., Endo T., Koike T., Amizuka N., Todoh M., Okumura J., Kajino T., Iwasaki N.
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Journal Title
Journal of Bone and Mineral Metabolism
Volume: ー
DOI
Related Report
Peer Reviewed
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[Journal Article] Involvement of distant octacalcium phosphate scaffolds in enhancing early differentiation of osteocytes during bone regeneration.2021
Author(s)
Saito S., Shiwaku Y., Hamai R., Hasegawa T., Sakai S., Tsuchiya K., Sai Y., Iwama R., Amizuka N., Takahashi T., Suzuki O.
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Journal Title
Acta Biomaterialia
Volume: 129巻
Pages: 309-322
DOI
Related Report
Peer Reviewed
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[Journal Article] Cardiotrophin Like Cytokine Factor 1 (CLCF1) alleviates excessive bone loss and osteoclast differentiation through activating interferon signaling and repressing the nuclear factor-κB signaling pathway.2021
Author(s)
Shunichi Yokota, Gen Matsumae, Tomohiro Shimizu, Tomoka Hasegawa, Taku Ebata, Daisuke Takahashi, Cai Heguo, Yuan Tian, Hend Alhasan, Masahiko Takahata, Ken Kadoya, Alaa Terkawi, Norimasa Iwasaki
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Journal Title
Bone
Volume: 153
Pages: 116140-116140
DOI
Related Report
Peer Reviewed / Int'l Joint Research
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