Parathyroid Hormone (1-34) Modulates Odontoblast Proliferation and Apoptosis via PKA and PKC-Dependent Pathways

Abstract

Parathyroid hormone (PTH) plays a key role in the development and homeostasis of mineralized tissues such as bone and dentine. We have reported that PTH (1-34) administration can increase dentine formation in mice and that this hormone modulates in vitro mineralization of odontoblast-like cells. The purpose of the present study was to investigate whether PTH (1-34) participates in the proliferative and apoptotic signaling of odontoblast-like cells (MDPC23). MDPC23 cells were exposed to 50 ng/ml hPTH (1-34) or vehicle for 1 (P1), 24 (P24), or 48 (P48) hours, and the cell proliferation, apoptosis, and cell number were evaluated. To examine whether changes in the proliferative and apoptotic signaling in response to PTH involve protein kinases A (PKA) and/or C (PKC), MDPC23 cells were exposed to PTH with or without PKC or PKA signaling pathway inhibitors. Overall, the results showed that the PKA pathway acts in response to PTH exposure maintaining levels of cell proliferation, while the PKC pathway is mainly involved for longer exposure to PTH (24 or 48 h), leading to the reduction of cell proliferation and increase of apoptosis. The exposure to PTH reduced the cell number in relation to the control group in a time-dependent manner. In conclusion, PTH modulates odontoblast-like cell proliferative and apoptotic response in a time-dependent manner. Both PKC and PKA pathways participate in PTH-induced modulation in an antagonist mode.

Intermittent Administration of Parathyroid Hormone 1–34 Enhances Osteogenesis of Human Mesenchymal Stem Cells by Regulating Protein Kinase Cδ

“…Prolonged PTH (1–34) exposure, for different durations, results in different degrees of PKC pathway stimulation [ 41 ]. Some studies have reported that PTH (1–34) exposure for 24 or 48 h results in the activation of the PKC pathway [ 42 ]. Therefore, PTH (1–34) activation, resulting in stimulation of either the PKC or PKA pathway, might be dependent on and influenced by PTH (1–34) treatment time, dose, absorption, and elimination or half-life.…”

Study of Dental Caries and PTH Gene

“…To the best of our knowledge, this is the first study to evaluate the association between SNPs in the PTH gene and dental caries in Brazilian children. PTH influences tooth formation, since the odontogenesis-related cells differentiate until dentin and enamel synthesis (4,6,7). There is evidence that odontoblasts, cementoblasts and ameloblasts, specific cells of tooth formation, express the PTH receptor 1 (PTHR1) and are sensible to PTH serum levels (7,24).…”

“…PTH influences tooth formation, since the odontogenesis-related cells differentiate until dentin and enamel synthesis (4,6,7). There is evidence that odontoblasts, cementoblasts and ameloblasts, specific cells of tooth formation, express the PTH receptor 1 (PTHR1) and are sensible to PTH serum levels (7,24). Although the effects of PTH on cementoblasts and ameloblasts are not fully understood (24), in vitro studies (7) and studies evaluating PTH-knockout mice (6) indicate that PTH modulates the proliferative and apoptotic responses of odontoblasts, suggesting that modifications in PTH serum levels during odontogenesis can affect dentine and enamel quality and increase the risk and progression of dental caries (6,7).…”

“…This process relies upon protein-cell interaction, in which odontoblasts and ameloblasts are the cells responsible for dentin and enamel synthesis (5). PTH play a direct role in odontoblast and ameloblast (6,7). Interestingly, during tooth formation, any imbalance in this network of protein-cell interaction may impacts dental tissues (8).…”

Effects of Intermittent Administration of Parathyroid Hormone (1‐34) on Bone Differentiation in Stromal Precursor Antigen‐1 Positive Human Periodontal Ligament Stem Cells

“…The time-dependent action of PTH might be due to differences in the signal transduction systems, indicating a synchronized regulation of cAMP/PKA and PKC signaling after PTH stimulation [ 39 ]. While the PKA pathway acts in response to short exposure to PTH, the PKC pathway is mainly involved at longer times of exposure in an antagonist mode [ 40 , 41 ]. In our study, STRO-1(+) PDLSCs were treated under the intermittent administration of PTH, which might be mediated predominantly by cAMP/PKA pathway.…”