Genetic evidence for the vital function of osterix in cementogenesis

Abstract

To date, attempts to regenerate a complete tooth, including the critical periodontal tissues associated with the tooth root, have not been successful. Controversy still exists regarding the origin of the cell source for cellular cementum (epithelial or mesenchymal). This disagreement may be partially due to a lack of understanding of the events leading to the initiation and development of the tooth roots and supportive tissues, such as the cementum. Osterix (OSX) is a transcriptional factor essential for osteogenesis, but its role in cementogenesis has not been addressed. In the present study, we first documented a close relationship between the temporal-and spatial-expression pattern of OSX and the formation of cellular cementum. We then generated 3.6 Col 1-OSX transgenic mice, which displayed accelerated cementum formation vs. WT controls. Importantly, the conditional deletion of OSX in the mesenchymal cells with two different Cre systems (the 2.3 kb Col 1 and an inducible CAG-CreER) led to a sharp reduction in cellular cementum formation (including the cementum mass and mineral deposition rate) and gene expression of dentin matrix protein 1 (DMP1) by cementocytes. However, the deletion of the OSX gene after cellular cementum formed did not alter the properties of the mature cementum as evaluated by backscattered SEM and resin-cast SEM. Transient transfection of Osx in the cementoblasts in vitro significantly inhibited cell proliferation and increased cell differentiation and mineralization. Taken together, these data support 1) the mesenchymal origin of cellular cementum (from PDL progenitor cells); 2) the vital role of OSX in controlling the formation of cellular cementum; and 3) the limited remodeling of cellular cementum in adult mice.

Scleraxis and osterix antagonistically regulate tensile force-responsive remodeling of the periodontal ligament and alveolar bone

“…In the PDL, the Scx + cell population represents a group of Osx is a zinc-finger-containing transcription factor that regulates the differentiation of pre-osteoblasts into fully functional osteoblasts (Nakashima et al, 2002). Genetic evidence suggests that Osx expression during tooth root formation is also closely associated with cementum formation (Cao et al, 2012). The number of Osx + cells in the PDL increase sharply in 4-to 6-week-old mice, whereas few Osx + cells are detected in the PDL of 6-month-old mice (Cao et al, 2012).…”

“…Genetic evidence suggests that Osx expression during tooth root formation is also closely associated with cementum formation (Cao et al, 2012). The number of Osx + cells in the PDL increase sharply in 4-to 6-week-old mice, whereas few Osx + cells are detected in the PDL of 6-month-old mice (Cao et al, 2012). Consistent with these findings, a number of Osx + cells were found in the developing PDL in 6-week-old mice, but Osx expression was decreased in the PDL of 12-week-old mice, the root formation of which is completed.…”

“…Osx is a zinc-finger-containing transcription factor that regulates the differentiation of pre-osteoblasts into fully functional osteoblasts and cementoblasts (Cao et al, 2012;Nakashima et al, 2002). Unlike bone formation, the molecular mechanisms governing ligament formation are not fully understood.…”

Haploinsufficiency of osterix in chondrocytes impairs skeletal growth in mice

“…These data suggest that Osx expressed in other cell types besides osteoblasts contribute to early embryonic skeletal development in mice. Furthermore, human genetic studies have shown that mutations in Osx are associated with skeletal diseases, thus implying a significant role for Osx in human skeletal development (3,15). Besides osteoblasts, pre-and hypertrophic chondrocytes have also been shown to express Osx albeit at a lower level (19).…”

From the Cover: Embryonic Exposure to TCDD Impacts Osteogenesis of the Axial Skeleton in Japanese medaka,Oryzias latipes

“…Moreover, children living in the TCDD-contaminated zones in Seveso, Italy display an increased incidence of tooth enamel defects (Alaluusua et al, 2004). Cementoblasts, the osteoblast-like cells responsible for forming of mineralized tissue surrounding the tooth-root surface, are regulated by OSX/SP7 (Cao et al, 2012), suggesting a possible linkage between TCDD exposure and altered dentition and bone formation observed in humans.…”