title: RUNX2 expression in developing human bones and various bone tumors.
abstract: The heterozygous germline mutation of runt-related protein 2 (RUNX2) causes cleidocranial dysplasia. To clarify the involvement of RUNX2 in human osteogenesis, fetal bones and various bone tumors were immunohistochemically examined. During both membranous and endochondral ossification in the fetus (n= 8), RUNX2 was expressed not only in osteoblastic cells but also in surrounding mesenchymal cells and early stage chondrocytes. Such an expression pattern was recapitulated in bone tumors: RUNX2 was unequivocally expressed in osteosarcoma (n= 20) and fibrous dysplasia (n= 10), regardless of the site of occurrence, cell morphology or amount of neoplastic osteoid. RUNX2 expression was limited to less differentiated cells in chondrogenic tumors (n= 20). We further analyzed whether RUNX2 expression was regulated by bone morphogenetic protein-2 (BMP-2), which is critical for osteoblastic differentiation. With real-time polymerase chain reaction, the RUNX2 mRNA level was correlated with BMP-2 mRNA level, and both levels were significantly higher in three osteosarcoma cell lines than in three chondrosarcoma cell lines. With treatment of recombinant BMP-2, the RUNX2 mRNA level was significantly altered in these cell lines. RUNX2 expression is constitutive in developing and neoplastic human osteogenesis, and is most likely to be regulated by BMP-2.
authors.affiliation: Departments of Pathology Orthopaedic Surgery, Yamagata University School of Medicine, Yamagata, Japan.
authors.forename: Masato
authors.initials: M
authors.lastname: Sugawara
authors.forename: Noriko
authors.initials: N
authors.lastname: Kato
authors.forename: Takashi
authors.initials: T
authors.lastname: Tsuchiya
authors.forename: Teiichi
authors.initials: T
authors.lastname: Motoyama
mesh_terms: D001846:Bone Development / Q000502:physiology*; D055396:Bone Morphogenetic Protein 2 / Q000235:genetics / Q000378:metabolism* / Q000494:pharmacology; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D019902:Chondrocytes / Q000378:metabolism; D002813:Chondrosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D050659:Core Binding Factor Alpha 1 Subunit / Q000235:genetics / Q000378:metabolism*; D005260:Female; D047109:Fetal Development; D005357:Fibrous Dysplasia of Bone / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D015972:Gene Expression Regulation, Neoplastic; D005865:Gestational Age; D006801:Humans; D010006:Osteoblasts / Q000378:metabolism; D012516:Osteosarcoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D012333:RNA, Messenger / Q000378:metabolism; D011994:Recombinant Proteins
chemical_list: C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D050659:Core Binding Factor Alpha 1 Subunit; D012333:RNA, Messenger; C493709:RUNX2 protein, human; D011994:Recombinant Proteins