Differential Effects of Fibromodulin Deficiency on Mouse Mandibular Bones and Teeth: A Micro-CT Time Course Study

Abstract

Fibromodulin (Fmod) is a keratan sulfate small leucine-rich proteoglycan which is enriched in bones and teeth. In order to determine its functions on bone and tooth mineralization we characterized the phenotype of Fmod-deficient (Fmod-KO) mice using a new-generation microfocus computerized tomography system (micro-CT) and software allowing advanced visualization of 3-D data. Three-week-old and 10- week-old Fmod-KO mandibles and teeth were compared with those of age-matched wild-type (WT) mice. In both young and mature mice the Fmod-KO mandibles were hypomineralized, especially the posterior (proximal) part of the mandible as it appeared to be the main target of the molecule deficiency whereas less extensive alterations were found in the alveolar bone. In transverse sections, larger marrow spaces were observed in the Fmod-KO mice compared with age-matched young or mature WT mice. Quantitative evaluation of the pulp volume of the first molar and 3-D reconstructions suggested that dentinogenesis was diminished in 3-week-old Fmod-KO teeth. In contrast, increased dentin formation was found in 10-week-old Fmod-KO mice and it was accompanied by a reduced pulp volume. Thus, the differential effects of Fmod deficiency on bones and teeth appear to diverge in adult mice. This may result from the previously reported differences in the molecular weight of Fmod in the 2 tissues or from compensatory mechanisms due to the overexpression of DSP and DMP-1 in the dental pulp of Fmod-KO. It is also possible that a single molecule plays diverging roles in a tissue-specific or region-specific manner.

Reduced phosphorus intake throughout gestation and lactation of sows is mitigated by transcriptional adaptations in kidney and intestine

“…Furthermore, FMOD (fibromodulin) and FN1 (fibronectin 1) were significantly down-regulated in L compared to the other groups. Fibromodulin plays a role in bone mineralization, and its deficiency causes osteoporosis [46]. Fibronectin, an extracellular matrix protein, plays an essential role in the initiation and progression of fibrillogenesis through interaction with other fibronectin molecules and extracellular matrix components such as collagens [47].…”

Mineral and Matrix Changes in Brtl/+Teeth Provide Insights into Mineralization Mechanisms

“…There is only one report of changes in mouse molar micro-CT parameters with age, in which fibromodulin-deficient mice at 3 weeks and 10 weeks were compared to wild type mice, and a reversal of phenotypic differences was found [24]. It is not clear from only two time points in each of the fibromodulin studies whether older animals begin to show degradation of their teeth or whether the KO animal's molars simply begin to approach the WT values as they age.…”

Enamel alterations in serotonin 2B receptor knockout mice

“…The X‐ray source was operated at 80 kV and 160 mA, with a 5 μm spatial resolution. Volume rendering, a technique for three‐dimensional (3D) visualization of samples, was suitable for rendering images from mouse mandibles acquired by micro‐CT and to identify the bone and different dental structures: pulp, dentin, and enamel (19). Volumetric measurements were carried out following the selection of a 3D volume of interest drawn around the first molar.…”