Targeted expression of csCSF-1 in op / op mice ameliorates tooth defects

• Published in: Archives of oral biology Vol. 52; no. 5; pp. 432 - 443
• Main Authors: Werner, S. Abboud, Gluhak-Heinrich, J, Woodruff, K, Wittrant, Y, Cardenas, L, Roudier, M, MacDougall, M
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.05.2007
• Subjects: Advanced Basic Science; Ameloblasts - metabolism; Amelogenesis Imperfecta - genetics; Amelogenin - analysis; Animals; Dental Enamel - abnormalities; Dental Enamel - pathology; Dentin - abnormalities; Dentin - pathology; Dentistry; Extracellular Matrix Proteins - analysis; Gene Expression Regulation - genetics; Gene Targeting - methods; Macrophage colony-stimulating factor (CSF-1); Macrophage Colony-Stimulating Factor - genetics; Mice; Mice, Transgenic; Odontoblasts - metabolism; Odontogenesis - genetics; Osteocalcin - genetics; Osteocalcin promoter; Osteopetrosis; Osteopetrosis - genetics; Phenotype; Promoter Regions, Genetic - genetics; Protein Isoforms - analysis; Receptor, Macrophage Colony-Stimulating Factor - analysis; Teeth; Tooth Abnormalities - genetics; Tooth Eruption - genetics; Transcription, Genetic - genetics; Transgenic mice; Osteopetrosis; Macrophage colony-stimulating factor (CSF-1); Osteocalcin promoter; Transgenic mice; Teeth
• ISSN: 0003-9969; 1879-1506
• DOI: 10.1016/j.archoralbio.2006.10.018

Abstract Objective The aim of this study was to characterize the tooth phenotype of CSF-1-deficient op / op mice and determine whether expression of csCSF-1 in these mice has a role in primary tooth matrix formation. Design Ameloblasts and odontoblasts, isolated from wt / wt frozen sections using laser capture microdissection, were analysed for csCSF-1, sCSF-1 and CSF-1R mRNA by RT-PCR. Mandibles, excised from 8 days op / op and wt / wt littermates, were examined for tooth morphology as well as amelogenin and DMP1 expression using in situ hybridisation. op / opCS transgenic mice, expressing csCSF-1 in teeth and bone using the osteocalcin promoter, were generated. Skeletal X-rays and histomorphometry were performed; teeth were analysed for morphology and matrix proteins. Results Normal dental cells in vivo express both CSF-1 isoforms and CSF-1R. Compared to wt / wt , op / op teeth prior to eruption showed altered dental cell morphology and dramatic reduction in DMP1 transcripts. op / opCS mice showed marked resolution of osteopetrosis, tooth eruption and teeth that resembled amelogenesis imperfecta-like phenotype. At 3 weeks, op / op teeth showed severe enamel and dentin defects and barely detectable amelogenin and DMP1. In op / opCS mice, DMP1 in odontoblasts increased to near normal and dentin morphology was restored; amelogenin also increased. Enamel integrity improved in op / opCS , although it was thinner than wt enamel. Conclusions Results demonstrate that ameloblasts and odontoblasts are a source and potential target of CSF-1 isoforms in vivo . Expression of csCSF-1 within the tooth microenvironment is essential for normal tooth morphogenesis and may provide a mechanism for coordinating the process of tooth eruption with endogenous matrix formation.