NF1 Gene Expression in Mouse Fracture Healing and in Experimental Rat Pseudarthrosis

Tommi Kuorilehto ¹, Erika Ekholm ¹, Marja Nissinen ¹, Kalevi Hietaniemi ¹, Ari Hiltunen ¹, Pekka Paavolainen ¹, Risto Penttinen ¹ and Juha Peltonen ^1*

¹ Department of Anatomy and Cell Biology (TK,MN,JP) and Department of Dermatology (JP), University of Oulu, Oulu, Finland; Department of Anatomy, Institute of Biomedicine (TK,JP), Department of Medical Biochemistry (EE,RP), and Department of Surgery (AH), University of Turku, Turku, Finland; Department of Orthopaedics and Traumatology, Helsinki University Central Hospital, Jorvi Hospital, Espoo, Finland (KH); and ORTON Orthopaedic Hospital of Invalid Foundation, Helsinki, Finland (PP)

^* To whom correspondence should be addressed. E-mail: juha.peltonen{at}utu.fi.

Submitted on July 17, 2005
Accepted on 14 November 2005

	Abstract

Neurofibromatosis type 1 (NF1) is an inherited disease with an incidence of 1:3000 worldwide. Approximately half of all patients with NF1 present osseous manifestations, which can vary from mild to severely debilitating changes, such as congenital pseudarthrosis. In the present study fracture healing of mouse tibia was followed and specimens were collected 5, 9, 14 and 22 days postoperatively. Experimental pseudarthrosis of rat was followed up to 15 weeks postoperatively. In situ hybridization and immunohistochemistry were used to demonstrate expression of NF1 tumor suppressor and phosphorylated p44/42 MAPK, an indicator of Ras-MAPK pathway. The results showed that ossified callus was formed in mouse fracture 22 days after operation. The final outcome of rat pseudarthrosis was detected 9 weeks after operation presenting abundant cartilaginous callus at the pseudarthrosis. NF1 gene expression was noted in the maturing and in the hypertrophic cartilages during normal mouse fracture healing, and in rat pseudarthrosis. Phosphorylated p44/42 MAPK was detected in a subpopulation of the hypertrophic chondrocytes in both models. Furthermore, positive labeling for NF1 mRNA and protein was detected in endothelium both in the pseudarthrosis and in the fracture. In conclusion, NF1 gene expression and function are needed for normal fracture healing, possibly restraining excessive Ras-MAPK pathway activation.

Key Words: neurofibromatosis type 1, fracture, pseudarthrosis, Ras, neurofibromin

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				J. Yan, S. Chen, Y. Zhang, X. Li, Y. Li, X. Wu, J. Yuan, A. G. Robling, R. Karpur, R. J. Chan, et al. Rac1 mediates the osteoclast gains-in-function induced by haploinsufficiency of Nf1 Hum. Mol. Genet., April 1, 2008; 17(7): 936 - 948. [Abstract] [Full Text] [PDF]

Guidelines | Subscriptions | About | exPRESS - Current - Archive | Business Information | Contact

The Journal of Histochemistry & Cytochemistry is owned, published, and licensed by The Histochemical Society © 2005