The BMP-2/BMP-7 heterodimer (BMP-2/-7) is a potent osteogenic inducer. It is well established that BMP-2/-7 activates mitogen activated protein kinases (MAPKs) in some cells. It is also widely accepted that MAPK signaling cascades play a crucial role in the immediate osteogenic response to BMPs. However, the precise mechanism and role of the MAPK signaling network in osteogenesis is still controversial since there are many kinds of BMP receptors (BMPR) whose signal transduction is very complex and whose signals differ from cell to cell. We investigated whether BMP-2/-7 regulates osteogenic gene expression in human periodontal ligament (HPDL) cells, and how MAPKs might be involved in this process, by treatment of HPDL cells with BMP-2/-7 with or without MAPK inhibitors. We found that the Jun-N-terminal kinase (JNK) is essential for the expression of almost all osteogenic marker genes. Inhibition of extracellular signal-regulated kinase (ERK) using inhibitor had no effect on the expression of early osteogenic marker genes, whereas it significantly downregulated the expression of late osteogenic marker genes such as Bone sialopotein and Osteocalcin. These results indicate that MAPKs play a crucial role in osteogenesis of HPDL cells.
Dens evaginatus is a rare dental anomaly characterized by the development of a tubercle on the occlusal surface of the tooth and can cause pulpitis, pulp necrosis, and periapical periodontitis due to tubercular fracture or attrition. Unlike with caries, pain caused by dens evaginatus may manifest itself in a distant location. Therefore, diagnosing the cause of that pain may prove problematic. Dens evaginatus usually occurs in the mandibular premolars. We report a successfully treated case in which dens evaginatus was difficult to diagnose due to distant radiation of pulpitis-induced pain. This pain occurred as a result of fracture of a tubercle located on the occlusal surface of the maxillary second molar, which is very rare.
Periodontal ligament (PDL) cells are composed of several different kinds of cells including mesenchymal stem cells (MSC). It is well known that these MSC play an important role in the regeneration of periodontal ligament and alveolar bone. The heterodimeric bone morphogenetic protein (BMP-2/-7) is a very potent BMP. However, BMP and TGF-1 signaling pathways that induce and regulate osteogenesis of HPDL cells are not well understood. It was reported that phosphatidylinositol 3-kinase (PI3K), which is activated by insulin-like growth factor-1 (IGF-1) and subsequently promotes the Akt phosphorylation, might play an important role in BMP-2/-7 and TGF-1-induced osteogenesis. There are numerous signaling pathways located downstream of PI3K/Akt, including the mTOR/p70S6K pathways that was the focus of this study. Here we show that TGF-1 is a more potent inducer of osteogenesis of HPDL cells than BMP-2/-7. LY294002, a PI3K inhibitor, and rapamycin, an inhibitor of mammalian target of rapamycin (mTOR), decreased both the Smad 3 phosphorylation and the osteogenic differentiation induced by TGF-1 treatment. In contrast, the phosphorylation of Smad1/5/ 8 by BMP-2/-7 treatment was affected by neither LY294002 nor rapamycin treatment and mTOR inhibition failed to reduce BMP-2/-7-induced osteogenesis of HPDL cells. Thus the PI3K -mTOR pathway is required for TGF-1-induced osteogenesis but is not essential for osteogenesis induced by BMP-2/-7. In conclusion, the PI3K/mTOR/p70S6K pathway plays different roles in the regulation of osteogenic differentiation by TGF-1 and BMP-2/-7.
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