PTHrP Induces Notch Signaling in Periodontal Ligament Cells

Abstract

Periodontal ligament (PDL) cells are known to play important roles in tooth eruption and alveolar bone metabolism. We previously reported that PTHrP increases RANKL expression in human PDL cells, suggesting that it promotes odontoclastic root resorption during tooth eruption. While it is known that Notch-related genes play a key role during bone development, the role of the Notch signaling pathway in PDL cells during tooth and bone resorption is less clear. We hypothesized that PTHrP induces a Notch ligand in PDL cells and thereby regulates osteo- and odontoclastogenesis. We found that PTHrP increased Notch1 ligand Jagged1 expression in human PDL cells in a dose- and time-dependent manner. PTHrP-induced Jagged1 up-regulation was mediated by PKA activation, but not by PKC. Jagged1 also promoted RANKL-induced osteoclastogenesis. These results demonstrate that PTHrP induces Jagged1 expression in PDL cells, leading to osteo- and odontoclastogenesis, and thus likely promoting tooth and alveolar bone resorption.

Enhanced adipogenic differentiation and reduced collagen synthesis induced by human periodontal ligament stem cells might underlie the negative effect of recombinant human bone morphogenetic protein-2 on periodontal regeneration

“…The cells from the collagen synthesis assay were used for a western blotting assay. Five days after initial treatment with rhBMP‐2, expression of types I, II, III and V collagen were confirmed by western blotting, as reported, with slight modifications (19). Confluent monolayers of cells on 100‐mm dishes were lysed in protein extraction reagent (M‐PER, Mammalian Protein Extraction Reagent; Pierce, Rockford, IL, USA) containing a protease inhibitor cocktail tablet (Complete EDTA‐free; Roche, Roche Diagnostics Gmbh Mannheim, Germany) and were collected with a cell scraper.…”

Molecular regulatory mechanism of tooth root development

“…Molecules such as TGF-β, Nfic, insulin-like growth factors, WNTs and fibroblast growth factors (FGFs) contribute to odontoblast and cementoblast terminal differentiation. 16,58,59,60,61,62,63 Bone morphogenetic proteins (BMPs) and Fgf signaling in the dental mesenchyme may participate in the induction of the HERS, because Bmp3, Bmp4 and Fgf10 are expressed strongly before root development. The number of roots and direction of root formation may also be influenced by the mesenchyme and structures derived from the mesenchyme.…”

“…16,58,59,60,61,62,63 We list the expression of various genes in different structures of the developing tooth root, including the dental epithelium (HERS), dental papilla and dental follicle (Table 1). …”

Notch Signaling Is Involved in Neurogenic Commitment of Human Periodontal Ligament-Derived Mesenchymal Stem Cells

“…Subsequently, the cleavage of Notch protein occurs intracellularly, resulting in the translocation of Notch intracellular domain (NICD) into the nucleus and further regulating Notch target gene expression [14]. In periodontal ligament cells, Notch signaling was shown to participate in osteogenic differentiation process and induction of osteoclastogenesis [4,15,16]. However, evidence of Notch signaling in hPDLSCs differentiation toward neuronal lineage is yet unknown.…”