In both cases,

i.e., incisor and molar, periostin functions inside the cell by interacting with the precursors of MMP-2 and 9 followed by proteolytic digestion to generate mature MMPs in their efficient secretion or by interacting with the precursor of Notch probably at the endoplasmic reticulum [15] for Notch1 stabilization and maturation, which is consistent with co-localization of Notch1 and periostin mRNAs in the outflow tract [32]. The putative molecular mechanisms of periostin in the periodontium are shown in Fig. 3. In addition, periostin also acts on the type I collagen production inside the cell, where periostin together Selleck GW572016 with tenascin-C forms a meshwork structure with fibronectin to constitute a scaffold MK 1775 for the cross-linking of type I collagen [15]. This cross-linking is effected by periostin in association with BMP-1 to activate lysyl oxidase for enhancement of cross-linking activity inside the cell [17]. On the other hand, periostin may also act outside the fibroblasts in the PDL, which cells produce collagen. This extracellular periostin may activate integrin or laminin on the PDL fibroblasts to promote their migration for remodeling of the PDL; because in the case of a myocardial infarction, periostin functions in the migration of cardiac fibroblasts by engaging integrin αvβ3 [24].

Also, in wound healing, periostin activates laminin γ2 on the basement membrane [18]. Consistent with this working hypothesis of extracellular action, Steffensen et al. found the expression of fibronectin, tenascin, laminin, and αv integrin in the periodontium [33]. 17-DMAG (Alvespimycin) HCl Furthermore, Popova et al. demonstrated that

α11β1 integrin regulates periodontal ligament function during incisor eruption, indicating the essential roles of integrin in cell migration of PDL fibroblasts and in collagen reorganization [34]. Although periostin has become an important molecular marker of the periodontal ligament and functions crucially in periodontal ligament regeneration, no diagnostic and clinical trials have begun yet in the dental field. However, recently, a diagnostic trial has been started in the pulmonary diseases, because periostin was shown to be a good biomarker of asthma. In patients with asthma, the high-Th2 phenotype has been associated with an increased level of circulating periostin induced by interleukin-13 (IL-13) and expressed by airway structural cells, which was detected by anti-periostin antibodies [35]. Recently, Corren et al. reported the effect of anti-IL-13 antibody, termed lebrikizumab, on asthma. Although there was a beneficial effect on airflow obstruction in all the patients who were treated with lebrikizumab, the effect was greater in patients who had circulating levels of periostin above the median and exhibited the high-Th2 phenotype that in those without this phenotype [36], indicating that periostin becomes a good biomarker for lebrikizumab treatment.