The short-lived exostosis induced surgically versus the lasting genetic hereditary multiple exostoses

Meirav Trebicz-Geffen, Zvi Nevo, Zoharia Evron, Natalia Posternak, Tova Glaser, Mati Fridkin, Yehuda Kollander, Dror Robinson

Research output: Contribution to journalArticlepeer-review

Abstract

Hereditary osteochondromas are often caused by mutation in the EXT1 gene. The lesions are typified by formation of a "pseudo" growth plate like lesion growing at 60° to the normal growth direction of the bone. Such lesions can be mimicked surgically by reverting the position - the polarity of the zone of LaCroix. The current study attempts to compare the pathology between EXT1 gene expression in humans and surgically created osteochondroma pathology in a rat model. Tissues of human bunion, human embryonal tissue, and human adult cartilage as well as normal rat epiphyses served as controls. Rats were operated on and a 60° span of the ring of LaCroix was inverted as described by Delgado (Delgado, E., Rodriguez, J. I., Serrada, A., Tellez, M., and Pariagoa, R., Clin. Orthop. 201, 251-258 (1985)). The surgically created osteochondromas were assessed by histology, histochemistry, and immunohistochemistry. The findings show that the surgically created lesions contain only a small amount of FGF receptor 3 (FGFR3) expressed on mesenchymal stem cells located in the perichondrium, as compared to the cell population carrying FGFR3 in the contralateral limb. Indian hedgehog and Bcl2 are downregulated, while BMP-2 is overexpressed in the operated limb, compared to the LaCroix ring of the contralateral limb. The shortage, as well as the disturbed migration routes, of the residual mesenchymal stem cells in surgically created osteochondromas leads eventually to resorption of the pathological elements. In search of additional markers characterizing such pathological structures composed of mesenchymal stem cells and cartilaginous and bony cells, EXT1 gene was found to be expressed in the surgically created osteochondromas, like in normal growth plates. Nitric oxide synthase was also expressed like in adult cartilage, though tumor necrosis factor α typifying Bunion formation was absent. In summary, surgically created osteochondromas lack the massive and continuous population of mesenchymal stem cells with Bcl2 expression. However, the small residual mesenchymal cell population gives rise to short-lived EXT1-expressing cells that disappear eventually due to spontaneous resorption.

Original languageEnglish
Pages (from-to)40-48
Number of pages9
JournalExperimental and Molecular Pathology
Volume74
Issue number1
DOIs
StatePublished - Feb 2003

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