Study of the pathophysiology of congenital pseudarthrosis of the tibia.

2004 Fiscal Year Final Research Report Summary

• 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 The University of Tokyo, Faculty of Medicine, Assistant, 医学部附属病院, 助手 (10262007)
• 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)
• Project Period (FY): 2002 – 2004
• Keywords: Osteoclast / RANKL / congenital pseudoarthrosis / Bone histomorphometry

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.

Research Products

• [Journal Article] Treatment of Congenital Pseudarthrosis of the Tibia : A Multicenter Study in Japan. (2005)
  • Author(s): Ohnishi T, Sato W, Matsuyama J, Yajima H, Haga N, Kamegaya M, Minami A, Sato M, Yoshino S, Oki T, Nakamura K.
  • Journal Title: J Peediatr Orthop 25 Pages: 219-224
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Treatment of Congenital Pseudarthrosis of the Tibia : A Multicenter Study in Japan. (2005)
  • Author(s): Ohnishi T, Sato W, Matsuyama J, Yajima H, Haga N, Kamegaya M, Minami A, Sato M, Yoshino S, Oki T, Nakamura K.
  • Journal Title: J Pediatr Orthop 25 Pages: 219-224
  • Description: 「研究成果報告書概要(欧文)」より
• [Journal Article] Signal transduction pathways regulating osteoclast differentiation and function. (2003)
  • Author(s): Tanaka, S., Nakamura, I., Inoue, J., Oda, I-I., Nakamura, K.
  • Journal Title: J Bone Miner Metab 21 Pages: 123-133
  • Description: 「研究成果報告書概要(和文)」より
• [Journal Article] Signal transduction pathways regulating osteoclast differentiation and function. (2003)
  • Author(s): Tanaka, S., Nakamura, I., Inoue, J., Oda, H., Nakamura, K.
  • Journal Title: J Bone Miner Metab 21 Pages: 123-133
  • Description: 「研究成果報告書概要(欧文)」より