Targeted expression of csCSF-1 in op/op mice ameliorates tooth defects.
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.
Werner
S Abboud
SA
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
Gluhak-Heinrich
J
J
Woodruff
K
K
Wittrant
Y
Y
Cardenas
L
L
Roudier
M
M
MacDougall
M
M
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
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