title: The short-lived exostosis induced surgically versus the lasting genetic hereditary multiple exostoses.
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 degrees 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 degree span of the ring of LaCroix was inverted as described by Delgado (Delgado, E., Rodriguez, J. I., Serada, 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 contralaetral 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 alpha 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.
authors.affiliation: Department of Clinical Biochemistry, Sackler School of Medicine, Tel Aviv University, Ramat Aviv, Tel Aviv 69978, Israel.
authors.forename: Meirav
authors.initials: M
authors.lastname: Trebicz-Geffen
authors.forename: Zvi
authors.initials: Z
authors.lastname: Nevo
authors.forename: Zoharia
authors.initials: Z
authors.lastname: Evron
authors.forename: Natalia
authors.initials: N
authors.lastname: Posternak
authors.forename: Tova
authors.initials: T
authors.lastname: Glaser
authors.forename: Mati
authors.initials: M
authors.lastname: Fridkin
authors.forename: Yehuda
authors.initials: Y
authors.lastname: Kollander
authors.forename: Dror
authors.initials: D
authors.lastname: Robinson
mesh_terms: D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000378:metabolism; D002356:Cartilage / Q000378:metabolism / Q000473:pathology*; D004195:Disease Models, Animal; D005097:Exostoses, Multiple Hereditary / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006614:Hindlimb / Q000000981:diagnostic imaging / Q000601:surgery; D006801:Humans; D017351:N-Acetylglucosaminyltransferases / Q000235:genetics* / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000378:metabolism; D052247:Nitric Oxide Synthase Type II; D015831:Osteochondroma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D011505:Protein-Tyrosine Kinases; D011859:Radiography; D051381:Rats; D051498:Receptor, Fibroblast Growth Factor, Type 3; D017468:Receptors, Fibroblast Growth Factor / Q000378:metabolism; D013234:Stem Cells / Q000473:pathology / Q000502:physiology; D016212:Transforming Growth Factor beta; D000099058:Exostosin 1
chemical_list: C525718:BMP2 protein, human; C525720:Bmp2 protein, rat; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D017468:Receptors, Fibroblast Growth Factor; D016212:Transforming Growth Factor beta; C496319:NOS2 protein, human; D019001:Nitric Oxide Synthase; D052247:Nitric Oxide Synthase Type II; C496318:Nos2 protein, rat; D017351:N-Acetylglucosaminyltransferases; D000099058:Exostosin 1; C496365:FGFR3 protein, human; D011505:Protein-Tyrosine Kinases; D051498:Receptor, Fibroblast Growth Factor, Type 3