Family with sequence similarity 20,-member C (FAM20C) is highly expressed in the mineralized tissues of mammals. Genetic studies showed that the loss-of-function mutations in FAM20C were associated with human lethal osteosclerotic bone dysplasia (Raine Syndrome), implying an inhibitory role of this molecule in bone formation. However, in vitro gain- and loss-of-function studies suggested that FAM20C promotes the differentiation and mineralization of mouse mesenchymal cells and odontoblasts. Recently, we generated Fam20c conditional knockout (cKO) mice in which Fam20c was globally inactivated (by crossbreeding with Sox2-Cre mice) or inactivated specifically in the mineralized tissues (by crossbreeding with 3.6 kb Col 1a1-Cre mice). Fam20c transgenic mice were also generated and crossbred with Fam20c cKO mice to introduce the transgene in the knockout background. In vitro gain- and loss-of-function were examined by adding recombinant FAM20C to MC3T3-E1 cells and by lentiviral shRNA–mediated knockdown of FAM20C in human and mouse osteogenic cell lines. Surprisingly, both the global and mineralized tissue-specific cKO mice developed hypophosphatemic rickets (but not osteosclerosis), along with a significant downregulation of osteoblast differentiation markers and a dramatic elevation of fibroblast growth factor 23 (FGF23) in the serum and bone. The mice expressing the Fam20c transgene in the wild-type background showed no abnormalities, while the expression of the Fam20c transgene fully rescued the skeletal defects in the cKO mice. Recombinant FAM20C promoted the differentiation and mineralization of MC3T3-E1 cells. Knockdown of FAM20C led to a remarkable downregulation of DMP1, along with a significant upregulation of FGF23 in both human and mouse osteogenic cell lines. These results indicate that FAM20C is a bone formation “promoter” but not an “inhibitor” in mouse osteogenesis. We conclude that FAM20C may regulate osteogenesis through its direct role in facilitating osteoblast differentiation and its systemic regulation of phosphate homeostasis via the mediation of FGF23.

The purpose of this research was to evaluate microdamage accumulation after mini-implant placement by self-drilling (without a pilot hole) and self-tapping (screwed into a pilot hole) insertion techniques. The null hypothesis was that the mini-implant insertion technique would have no influence on microcrack accumulation and propagation in the cortical bones of the maxillae and mandibles of adult hounds. Mini-implants (n = 162; diameter, 1.6 mm; length, 6 mm) were placed in the maxillae and mandibles of 9 hounds (12-14 months old) with self-drilling and self-tapping insertion techniques. The techniques were randomly assigned to the left or the right side of each jaw. Each hound received 18 mini-implants (10 in the mandible, 8 in the maxilla). Histomorphometric parameters including total crack length and crack surface density were measured. The null hypothesis was rejected in favor of an alternate hypothesis: that the self-drilling technique results in more microdamage (microcracks) accumulation in the adjacent cortical bone in both the maxilla and the mandible immediately after mini-implant placement. A cluster level analysis was used to analyze the data on the outcome measured. Since the measurements were clustered within dogs, a paired-samples t test was used to analyze the average differences between insertion methods at both jaw locations. A significance level of 0.05 was used for both analyses. The self-drilling technique resulted in greater total crack lengths in both the maxilla and the mandible (maxilla: mean difference, 18.70 ± 7.04 μm/mm2; CI, 13.29-24.11; mandible: mean difference, 22.98 ± 6.43 μm/mm2; CI, 18.04-27.93; P <0.05), higher crack surface density in both the maxilla and the mandible (maxilla: mean difference, 10.39 ± 9.16 μm/mm2; CI, 3.34-17.43; mandible: mean difference, 11.28 ± 3.41 μm/mm2; CI, 8.65-13.90; P <0.05). This study demonstrated greater microdamage in the cortical bones of adult hounds in both the maxilla and the mandible by the self-drilling insertion technique compared with the self-tapping technique.

Residual dental follicles surrounding the crowns of impacted teeth may represent a significant risk for their potential pathological changes. In this study, the expression levels of cell cycle proteins, proliferating cell nuclear antigen (PCNA), cyclin D1, and p21 were evaluated using immunohistochemistry. Twenty-two impacted mandibular third molars in 17 healthy individuals were evaluated in this study. They were divided into two groups on the basis of the depth of impaction: the partially impacted group and the fully impacted group. The impacted teeth were surgically removed and the surrounding follicle was curetted and examined by immunohistochemistry to evaluate whether there was a difference in cell cycle regulation between the two groups. PCNA was expressed in most of the epithelial cells with no significant difference between the groups. The p21 expression was significantly higher in the full bony impaction group. Cyclin D1 expression was expressed at low levels with no significant difference between the groups. Weak cyclin D1 expression was consistent with high p21, a negative regulator of the cell cycle. The high p21 expression could be a compensatory mechanism to the high PCNA levels. These results suggest the possibility that dental follicles associated with full bony impactions possess different cellular activities compared with partial bony/soft-tissue impactions.