Project/Area Number |
14571362
|
Research Category |
Grant-in-Aid for Scientific Research (C)
|
Allocation Type | Single-year Grants |
Section | 一般 |
Research Field |
Orthopaedic surgery
|
Research Institution | The University of Tokyo |
Principal Investigator |
HIRAOKA Hisatada (2004) The University of Tokyo, Faculty of Medicine, Assistant, 医学部附属病院, 助手 (10262007)
滝川 一晴 (2003) 東京大学, 医学部附属病院, 助手 (80360866)
筋野 隆 (2002) 東京大学, 医学部附属病院, 助手 (40344452)
|
Co-Investigator(Kenkyū-buntansha) |
HOSHI Kazuto The University of Tokyo, Faculty of Medicine, Associate Professor, 医学部附属病院, 寄付講座教員(客員助教授) (30344451)
MATSUDAIRA Koh The University of Tokyo, Faculty of Medicine, Assistant, 医学部附属病院, 助手 (10302697)
NAKAMURA Kozo The University of Tokyo, Faculty of Medicine, Professor, 医学部附属病院, 教授 (60126133)
岡崎 裕司 東京大学, 医学部附属病院, 講師 (30241988)
平岡 久忠 東京大学, 医学部附属病院, 助手 (10262007)
滝川 一晴 東京大学, 医学部附属病院, 助手
|
Project Period (FY) |
2002 – 2004
|
Project Status |
Completed (Fiscal Year 2004)
|
Budget Amount *help |
¥3,700,000 (Direct Cost: ¥3,700,000)
Fiscal Year 2004: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2003: ¥500,000 (Direct Cost: ¥500,000)
Fiscal Year 2002: ¥2,700,000 (Direct Cost: ¥2,700,000)
|
Keywords | Osteoclast / RANKL / congenital pseudoarthrosis / Bone histomorphometry / 先天性脛骨偽関節賞 / 小児難治性疾患 / 先天性脛骨偽関節症 / ランクリガンド |
Research Abstract |
This project investigated the possible pathophysiology of congenital pseudarthrosis of the tibia, one of the most controversial pediatric entities in terms of etiopathogenesis, pathology, and treatment. Eight patients with this disease and seven adult patients with post-traumatic pseudarthrosis as a control were reviewed histologically, using pathologic materials. The area of congenital pseudarthrosis was divided into three parts with different morphological features ; a highly cellular, fibromatosis area, a cartilagenous area and an osseous area. Interestingly, a marked number of osteoclasts, tartrate resistant acid phosphatase-positive multinucleated cells were detected on the surface of the bone and cartilage, and even in the fibrous area apart from bone surfaces. Bone histomorphometric analysis revealed that in congenital pseudarthrosis, osteoclast number (N. Oc/BS) and osteoclast surface (Oc. S/BS) were 2.66 +/-0.92 [/mm](mean +/-SD) and 10.67 +/-4.86%, respectively, while in the case of adult pseudarthrosis, N. Oc/BS and Oc. S/BS were 0.62 +/-0.33 [/mm] and 2.28 +/-1.20%, respectively. Furthermore, immunohistochemical study showed that RANK ligand, an essential factor for osteoclastogenesis, was highly expressed not only in the fibroblastic cells but also osteoclasts themselves in congenital pseudarthrosis. RT-PCR analysis also revealed the higher expression of RANK ligand in congenital pseudarthrosis of the tibia than in post-traumatic pseudoarthrosis. Taken together, the enhanced osteoclastogenesis is at least in part involved in the pathophysiology of congenital pseudarthrosis of the tibia. In addition, RANK ligand, an autocrine and paracrine factor for osteoclast differentiation and activation, might be one of the therapeutic targets for this refractory disease.
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