title: Targeted expression of csCSF-1 in op/op mice ameliorates tooth defects.
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.
  
  
  METHODS
  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.
authors.affiliation: Department of Pathology, University of Texas Health Science Center, 7703 Floyd Curl Drive and South Texas Veteran's Health Care System, Audi L. Murphy Division, San Antonio, TX 78229, USA. abboudwerner@uthscsa.edu
authors.forename: S Abboud
authors.initials: SA
authors.lastname: Werner
authors.forename: J
authors.initials: J
authors.lastname: Gluhak-Heinrich
authors.forename: K
authors.initials: K
authors.lastname: Woodruff
authors.forename: Y
authors.initials: Y
authors.lastname: Wittrant
authors.forename: L
authors.initials: L
authors.lastname: Cardenas
authors.forename: M
authors.initials: M
authors.lastname: Roudier
authors.forename: M
authors.initials: M
authors.lastname: MacDougall
mesh_terms: D000565:Ameloblasts / Q000378:metabolism; D000567:Amelogenesis Imperfecta / Q000235:genetics; D053523:Amelogenin / Q000032:analysis; D000818:Animals; D003743:Dental Enamel / Q000002:abnormalities / Q000473:pathology; D003804:Dentin / Q000002:abnormalities / Q000473:pathology; D016326:Extracellular Matrix Proteins / Q000032:analysis; D005786:Gene Expression Regulation / Q000235:genetics*; D018390:Gene Targeting / Q000379:methods*; D016173:Macrophage Colony-Stimulating Factor / Q000235:genetics*; D051379:Mice; D008822:Mice, Transgenic; D009804:Odontoblasts / Q000378:metabolism; D009805:Odontogenesis / Q000235:genetics*; D015675:Osteocalcin / Q000235:genetics; D010022:Osteopetrosis / Q000235:genetics*; D010641:Phenotype; D011401:Promoter Regions, Genetic / Q000235:genetics; D020033:Protein Isoforms / Q000032:analysis; D016186:Receptor, Macrophage Colony-Stimulating Factor / Q000032:analysis; D014071:Tooth Abnormalities / Q000235:genetics*; D014078:Tooth Eruption / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D053523:Amelogenin; C513308:Dmp1 protein, mouse; D016326:Extracellular Matrix Proteins; D020033:Protein Isoforms; D015675:Osteocalcin; D016173:Macrophage Colony-Stimulating Factor; D016186:Receptor, Macrophage Colony-Stimulating Factor