A Novel Role of Periostin in Postnatal Tooth Formation and Mineralization

Abstract

Periostin plays multiple functions during development. Our previous work showed a critical role of this disulfide-linked cell adhesion protein in maintenance of periodontium integrity in response to occlusal load. In this study, we attempted to address whether this mechanical response molecule played a direct role in postnatal tooth development. Our key findings are 1) periostin is expressed in preodontoblasts, and odontoblasts; and the periostin-null incisor displayed a massive increase in dentin formation after mastication; 2) periostin is also expressed in the ameloblast cells, and an enamel defect is identified in both the adult-null incisor and molar; 3) deletion of periostin leads to changes in expression profiles of many non-collagenous protein such as DSPP, DMP1, BSP, and OPN in incisor dentin; 4) the removal of a biting force leads to reduction of mineralization, which is partially prevented in periostin-null mice; and 6) both in vitro and in vivo data revealed a direct regulation of periostin by TGF-␤1 in dentin formation. In conclusion, periostin plays a novel direct role in controlling postnatal tooth formation, which is required for the integrity of both enamel and dentin.It is well known that mechanical loading stimulates new bone formation, whereas unloading or disuse of bone (e.g. longtime bed rest, spaceflight, or cast immobilization) accelerates bone resorption. This adaptation is critical for bone modeling and remodeling (1). The anabolic degree to which the bone responds to physical activity has being associated with the intensity and loading magnitude of the exercise. Under normal conditions, strenuous exercise such as weightlifting yields thicker and denser bone compared with jogging and swimming; the latter two types of exercise are less forceful and produce less mechanical stimulus (2). A well-designed study by Tatsumi et al. (3) demonstrated that osteocytes are the key sensor controlling both bone formation and bone resorption in the unloading animal model. The accumulated evidence supports a recommendation by the National Osteoporosis Foundation: regular weight-bearing and muscle strengthening exercise is an effective countermeasure to fight against osteoporosis, a silent bone loss in the elderly population worldwide.The development and maintenance of the dental and periodontal structures are also directly influenced by mechanical stimuli (4). This stimulation can be the result of normal occlusal function or orthodontic treatment. It is well documented that during orthodontic treatment, tension on the side from which a tooth moves away results in the formation of new bone (i.e. osteogenic), while compression on the opposite site leads to bone resorption. This relationship seems contrary to the situation in the long bone where the loaded site is osteogenic and the unloaded site is resorptive (5). One of the interpretations regarding this difference between the alveolar bone and long bone is that the periodontal ligament (PDL), 3 a soft tissue located between the teeth and alveolar bone,...

Mohawk transcription factor regulates homeostasis of the periodontal ligament

“…In keeping with the findings of the PDL analysis in Mkx −/− mice, gene expression analysis in MKXsilencing and Mkx-overexpression experiments using hPDL fibroblasts revealed that MKX strongly and specifically promotes the expression of a set of extracellular matrix genes related to PDL tissue formation, including COL1A1 and COL1A2, which are similar to those reported in mesenchymal stem cells (Liu et al, 2015;Otabe et al, 2015). In particular, in PDL cells, Postn, which is among the extracellular matrix adhesion molecules mainly expressed in the bone, periosteum, and PDL tissues (KruzynskaFrejtag et al, 2004;Ma et al, 2011;Rios et al, 2005), was significantly decreased in the M1 PDL in 10-week-old Mkx −/− mice in vivo. In addition, Postn-deficient mice exhibit a phenotype of vertical PDL expansion and alveolar bone resorption in the M1 furcation area (Horiuchi et al, 1999;Rios et al, 2008), suggesting that PDL phenotype in Mkx −/− mice could, in part, be due to the suppression of Postn.…”

“…Although the PDL is composed of heterogeneous cell types such as fibroblasts, osteoblasts, osteoclasts, cementoblasts, endothelial cells, sensory cells and their progenitor or stem cells (Beertsen et al, 1997;Maeda et al, 2011;Ueda-Maeda, 2006), fibroblasts are responsible for the fibrous attachment of the PDL. The components of PDL include type I collagen (70-80%), other types of collagen (type III, IV, V, VI and XII collagens), and other extracellular matrix proteins such as periostin (Postn), glycoproteins and proteoglycans, all of which are mainly produced by PDL fibroblasts (Aukkarasongsup et al, 2013;Beertsen et al, 1997;Ma et al, 2011;Rios et al, 2005;Sloan, 1979;Ahuja, 2012).…”

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

“…Scx is also a member of the twist subfamily of basic helix-loophelix transcription factors (Atchley and Fitch, 1997). The inhibitory action of Pstn on mineralization was reported using an odontoblastic cell line (Ma et al, 2011). We found that not only Scx but also Pstn were significantly upregulated on the tensile force-loaded site of the PDL.…”

“…For a more detailed analysis, we compared the expression of periostin (Pstn; Postn -Mouse Genome Informatics), a major ECM component of the PDL (Ma et al, 2011), with the expression of Scx. In a maxillary second molar of a 6-week-old ScxGFP Tg mouse, Pstn was localized to the gingival lamina propria (red arrowheads in Fig.…”

<b>Hertwig’s epithelial root sheath cells contribute to formation of periodontal ligament through epithelial-mesenchymal transition by </b><b>TGF-β </b>

“…Periostin, initially identified as osteoblast-specific factor 2, secreted from osteoblasts (23), is specifically expressed in collagen-rich fibrous connective tissues such as PDL (21). Adult periostin null mice were shown to exhibit a periodontal disease phenotype including external root resorption caused by collagen fibril disorganization with defective fibronectin expression (17,22). Additionally, it has been reported that TGF-β can increase periostin expression in PDL (27).…”