Fibromodulin is Implicated in Bones and Teeth Mineralization

M. Goldberg*(1), A. Marchadier(2), D. Septier(1) , H. Cherifi (1) , C. Vidal(2), R. Sugars(3), A. Oldberg(4) T. Kilts(5) M. Young(5) Fibromodulin: a KS-Small Leucine-Rich Proteoglycan Implicated in the Mineralization of Bones and Teeth. 1) EA2496, Paris Descartes France, 2) INSERM U747, France, 3) Center for Oral Biology, Dept. Dental Med. Karolinska Institut, Stockholm Sweden, 4) University of Lund, Sweden, 5) NIDCR, NIH Bethesda, MD USA.

Small leucine-rich proteoglycans are components of the extracellular matrix of mineralized tissues. DS/CSPGs (i.e. decorin and biglycan) and KSPGs (i.e. lumican, osteoadherin and fibromodulin, or Fmod) have been found in dentin, cementum and bone. However, the role these PGs might have in promoting or inhibiting mineralization is still unclear.

Western blotting revealed that the Fmod MW was higher in bone (52kDa) compared with with dental tissues (52 and 40kDa). Strong immunostaining of Fmod was restricted to i) the distal border of secretory odontolblasts, ii) the distal junctional complex of secretory ameloblasts, iii) the stratum intermedium and there was faint staining in the predentin.

Fmod deficient (KO) tissues have collagen fibrils with a larger diameter than controls (WT). Dentin was also hypomineralized in the Fmod KO. In molars, the pulp chambers were wider in the KO compared to WT, and the observed differences in dentin formation were confirmed by X-ray microcomputed tomography. Structural defects were observed within the forming enamel in the incisor of the KO mice. Compensatory mechanisms appeared to partially hide the defects of dental tissues, most likely by DSP, DMP-1 and BSP which were over-expressed, but not by OPN which showed no differences between the WT and KO tissues.

Using the scanning electron microscopy, backscattering analysis of sections of mandibles of day 21 mice revealed larger surfaces occupied by the bone medulla in the KO. X-ray tomography revealed severe hypomineralization of bone, mostly in the distal part of the mandible of KO mice, including the condyle, coronoïd, angula and the vertical branch, The alveolar bone located in the central part was also defective, whereas changes were more subtle in the anterior (rostral) part. The bone deficiency in the KO was even more severe in 10 weeks- old mice.

Altogether, these data suggest that Fmod is a crucial factor in regulating mineralization. We delineate the differences between the three different parts of the mandibular bone, as well as differences between bone and tooth tissues.