ABSTRACT
Dietary salt uptake and inflammation promote sodium accumulation in tissues, thereby modulating cells like macrophages and fibroblasts. Previous studies showed salt effects on periodontal ligament fibroblasts and on bone metabolism by expression of nuclear factor of activated T-cells-5 (NFAT-5). Here, we investigated the impact of salt and NFAT-5 on osteoclast activity and orthodontic tooth movement (OTM). After treatment of osteoclasts without (NS) or with additional salt (HS), we analyzed gene expression and the release of tartrate-resistant acid phosphatase and calcium phosphate resorption. We kept wild-type mice and mice lacking NFAT-5 in myeloid cells either on a low, normal or high salt diet and inserted an elastic band between the first and second molar to induce OTM. We analyzed the expression of genes involved in bone metabolism, periodontal bone loss, OTM and bone density. Osteoclast activity was increased upon HS treatment. HS promoted periodontal bone loss and OTM and was associated with reduced bone density. Deletion of NFAT-5 led to increased osteoclast activity with NS, whereas we detected impaired OTM in mice. Dietary salt uptake seems to accelerate OTM and induce periodontal bone loss due to reduced bone density, which may be attributed to enhanced osteoclast activity. NFAT-5 influences this reaction to HS, as we detected impaired OTM and osteoclast activity upon deletion.
Subject(s)
Alveolar Bone Loss/metabolism , Osteoclasts/metabolism , Osteogenesis , Sodium Chloride, Dietary/metabolism , Tooth Migration/metabolism , Animals , Bone Density , Bone Remodeling , Male , Mice , Osteoclasts/cytology , Periodontal Ligament/metabolism , RAW 264.7 Cells , Tartrate-Resistant Acid Phosphatase/metabolism , Transcription Factors/metabolismABSTRACT
Mechanical force loading exerts important effects on the skeleton by controlling bone mass and strength. Several in vivo experimental models evaluating the effects of mechanical loading on bone metabolism have been reported. Orthodontic tooth movement is a useful model for understanding the mechanism of bone remodeling induced by mechanical loading. In a mouse model of orthodontic tooth movement, TNF-α was expressed and osteoclasts appeared on the compressed side of the periodontal ligament. In TNF-receptor-deficient mice, there was less tooth movement and osteoclast numbers were lower than in wild-type mice. These results suggest that osteoclast formation and bone resorption caused by loading forces on the periodontal ligament depend on TNF-α. Several cytokines are expressed in the periodontal ligament during orthodontic tooth movement. Studies have found that inflammatory cytokines such as IL-12 and IFN-γ strongly inhibit osteoclast formation and tooth movement. Blocking macrophage colony-stimulating factor by using anti-c-Fms antibody also inhibited osteoclast formation and tooth movement. In this review we describe and discuss the effect of cytokines in the periodontal ligament on osteoclast formation and bone resorption during mechanical force loading.
Subject(s)
Bone Resorption/metabolism , Cytokines/metabolism , Osteoclasts/metabolism , Periodontium/metabolism , Stress, Mechanical , Tooth Migration/metabolism , Animals , Bone Remodeling/physiology , Bone Resorption/pathology , Humans , Osteoclasts/pathology , Periodontal Ligament/metabolism , Periodontal Ligament/pathology , Periodontium/pathology , Tooth Migration/pathologyABSTRACT
The relapse of teeth that have moved during orthodontic treatment is a major clinical issue with respect to the goals of successful treatment. Relaxin has an influence on many physiologic processes, such as collagen turnover. In this study, we determined the effects of relaxin on the relapse and remodeling of periodontal tissue after experimental tooth movement in rats, and we explored the molecular mechanism underlying these processes. To induce experimental tooth movement in rats, 10 g of orthodontic force was applied to the molars. After 14 days, the spring was removed, and then animals began receiving relaxin at a dose of 500 ng/ml for 1 week. The results were evaluated by micro-computed tomography and immunofluorescence staining. In addition, the effects of matrix metalloproteinase (MMP)-1 and MMP-8 production were investigated in human periodontal ligament (hPDL) cells in vitro. The expression of MMP-1 and MMP-8 was analyzed by real-time polymerase chain reaction and enzyme-linked immunosorbent assay. Furthermore, we demonstrated the signaling pathways involved in relaxin-regulated MMPs expression. The relapse distances and percentages were significantly decreased in the experimental group compared with the controls in vivo. A double-immunofluorescence analysis for Col-I/MMP-1 and Col-I/MMP-8 detected the expression of relaxin in the PDL. Relaxin significantly increased the MMP-1 and MMP-8 expression in a time-dependent manner in hPDL cells in vitro. Furthermore, a p38 inhibitor (SB203580) significantly inhibited the MMP-1 and MMP-8 expression. Our results indicated that relaxin modulates the collagen metabolism, and this hormone may therefore be useful to prevent orthodontic relapse following orthodontic treatment.
Subject(s)
Periodontal Ligament/drug effects , Relaxin/pharmacology , Tooth Migration/drug therapy , Adolescent , Animals , Cell Survival/drug effects , Cells, Cultured , Collagen Type I/metabolism , Disease Models, Animal , Enzyme Inhibitors/pharmacology , Female , Gene Expression Regulation, Enzymologic , Humans , Imidazoles/pharmacology , Male , Matrix Metalloproteinase 1/genetics , Matrix Metalloproteinase 1/metabolism , Matrix Metalloproteinase 8/genetics , Matrix Metalloproteinase 8/metabolism , Matrix Metalloproteinase Inhibitors , Periodontal Ligament/metabolism , Periodontal Ligament/pathology , Pyridines/pharmacology , RNA, Messenger/metabolism , Rats , Rats, Wistar , Recurrence , Relaxin/metabolism , Tooth Migration/metabolism , Tooth Migration/pathology , X-Ray MicrotomographyABSTRACT
Compressive force during orthodontic tooth movement induces osteoclast formation in vivo. TNF-α plays an important role in mouse osteoclast formation and bone resorption induced by compressive force during orthodontic tooth movement. Stromal cells, macrophages and T cells take part in TNF-α-induced osteoclast formation in vitro. Root resorption caused by odontoclasts is a major clinical problem during orthodontic tooth movement. In this study, we determined the cell type targeted by TNF-α during compressive-force-induced osteoclast and odontoclast formation to elucidate the mechanism of bone and root resorption in vivo. An orthodontic tooth movement mouse model was prepared with a nickel-titanium closed coil spring inserted between the maxillary incisors and the first molar. Using TNF receptor 1- and 2-deficient (KO) mice, we found that osteoclast and odontoclast formation was mediated by TNF-α in orthodontic tooth movement. We generated four types of chimeric mice: wild-type (WT) bone marrow cells transplanted into lethally irradiated WT mice (WT>WT), KO bone marrow cells transplanted into lethally irradiated WT mice (KO>WT), WT bone marrow cells transplanted into lethally irradiated KO mice (WT>KO), and KO marrow cells transplanted into lethally irradiated KO mice (KO>KO). Using anti-CD4 and anti-CD8 antibodies, T cells were eliminated from these mice. We subjected these chimeric mice to orthodontic tooth movement. Orthodontic tooth movement was evaluated and tartrate-resistant acid phosphatase-positive cells along the alveolar bone (osteoclasts) and along the tooth root (odontoclasts) were counted after 12 days of tooth movement. The amount of orthodontic tooth movement, and the number of osteoclasts and odontoclasts on the compression side were significantly lower in WT>KO and KO>KO mice than in WT>WT and KO>WT mice. According to these results, we concluded that TNF-α-responsive stromal cells are important for osteoclast and odontoclast formation during orthodontic tooth movement.
Subject(s)
Osteoclasts/cytology , Stromal Cells/cytology , Tooth Migration/metabolism , Tumor Necrosis Factor-alpha/metabolism , Animals , Disease Models, Animal , Male , Mice , Osteoclasts/metabolism , Receptors, Tumor Necrosis Factor, Type I/deficiency , Receptors, Tumor Necrosis Factor, Type II/deficiency , Stromal Cells/metabolismABSTRACT
OBJECTIVE: This study aimed to investigate the inhibitory effect of Odanacatib on orthodontic recurrence in rats. MATERIALS AND METHODS: Forty rats were selected to establish a planting anchorage molar movement model, and 50 g of force was used for the mesial movement of the right maxillary first molar. Forty rats were randomly divided into the observation group (n=20) and control group (n=20). Odanacatib (60 µl, 1.25 µM) was locally injected into the mucoperiosteum around the right maxillary first molar of rats in the experimental group, and an equal amount of normal saline was injected into rats in the control group. A Vernier caliper was used for measuring the recurrence movement distance and recurrence rate of rats, Micro-CT for scanning the bone mineral density (BMD) and bone volume fraction (BVF) of the alveolar bone, TRAP special staining for observing changes in osteoclasts and quantitative Real Time-Polymerase Chain Reaction (qRT-PCR) for detecting the mRNA expressions of cathepsin K (CatK) and insulin-like growth factor 1 (IGF-1) in periodontal tissues. RESULTS: After 3 weeks of modeling, the movement distance of the first molar of rats in the two groups was 1.16±0.19 mm. The molar movement distance and recurrence rate of rats were significantly higher in the control group than those in the observation group (p<0.05). The BMD and BVF of the alveolar bone of rats were markedly lower in the control group than those in the observation group (p<0.05). There was no statistically significant difference in the number of osteoclasts between the observation group (26.15±3.92) and the control group (27.01±2.74) (t=0.882, p=0.383). The CatK mRNA expression of rats was remarkably lower in the observation group than that in the control group (p<0.05). The IGF-1 mRNA expression of rats was significantly higher in the observation group than that in the control group (p<0.05). CONCLUSIONS: By promoting the IGF-1 mRNA expression and increasing the BMD and BVF of the alveolar bone, Odanacatib inhibits orthodontic recurrence and has no effect on osteoclast activity.
Subject(s)
Biphenyl Compounds/therapeutic use , Cathepsin K/antagonists & inhibitors , Insulin-Like Growth Factor I/antagonists & inhibitors , Osteoclasts/drug effects , Tooth Migration/drug therapy , Tooth Movement Techniques/methods , Alveolar Process/diagnostic imaging , Alveolar Process/drug effects , Animals , Biphenyl Compounds/administration & dosage , Cathepsin K/genetics , Disease Models, Animal , Insulin-Like Growth Factor I/genetics , Mesial Movement of Teeth/drug therapy , Osteoclasts/metabolism , Periodontium/drug effects , Periodontium/metabolism , RNA, Messenger/genetics , Rats, Inbred Strains , Recurrence , Tooth Migration/metabolism , X-Ray MicrotomographyABSTRACT
The purpose of this study was to investigate expression of type I collagen and bone sialoprotein (BSP) mRNAs in the alveolar bone accompanied with tooth movement. The right side of the upper jaw of the rat was used for orthodontic tooth movement, and the left side was used for physiological tooth movement. After the proper number of days of movement, histological specimens were decalcified and sliced into paraffin sections. The expression of mRNAs was examined by the in situ hybridization method. In the samples of physiological tooth movement, a high level of expression in both mRNAs was observed in osteoblasts along the mineralization front and adjacent osteocytes in the interradicular septum (IRS). In contrast, a low level of mRNA expression was observed on the opposite side of the IRS. In the specimens of experimental tooth movement, a high level of expression was detected in the osteoblasts on the tension side of IRS, but negligible reaction in those on the compression side. These results suggest that BSP gene expression as well as that of collagen are related not only to mineralization in physiological bone remodeling but also to the process by activated osteoblasts induced by orthodontic force. In addition, response to the artificial force was observed in osteocytes in IRS.
Subject(s)
Bone Remodeling/physiology , Collagen/genetics , Periodontium/metabolism , RNA, Messenger/analysis , Sialoglycoproteins/genetics , Tooth Migration/metabolism , Tooth Movement Techniques , Animals , In Situ Hybridization , Integrin-Binding Sialoprotein , Male , Rats , Rats, Sprague-DawleyABSTRACT
Orthodontic tooth movement is recognized as a pro-inflammatory stressor of human periodontal ligament (hPDL) cells. However, the cell-signaling pathways linking interleukin-8 (IL-8), intercellular adhesion molecule-1 (ICAM-1), pro-inflammatory cytokines, and dexamethasone in hPDL cells have not been well elucidated. In this study, we investigated the role of mitogen-activated protein (MAP) kinases in dexamethasone- and TNF-alpha-induced IL-8 and ICAM-1 expression in hPDL cells. IL-8 production was measured by enzyme-linked immunosorbent assay (ELISA) and reverse transcriptase-polymerase chain reaction (RT-PCR) analysis. MAP kinase activation and IkappaB degradation were determined by Western blot analysis, and ICAM-1 expression was determined by RT-PCR and FACS analysis. TNF-alpha increased IL-8 mRNA expression and protein secretion in a dose- and time-dependent manner. Dexamethasone suppressed TNF-alpha-induced IL-8 production in a dose-dependent manner. In addition, dexamethasone inhibited TNF-alpha-induced phosphorylation of p38 MAP kinase and extracellular-regulated kinases (ERKs), IkappaB degradation, and NF-kappaB activation. Selective inhibitors for ERKs and p38 attenuated TNF-alpha-induced IL-8 and ICAM-1 expression in the presence and absence of dexamethasone, indicating that MAP kinases play a role in the response of hDPL cells to TNF-alpha. Furthermore, these results suggest that inflammatory cytokine- and dexamethasone-induced IL-8 and ICAM-1, produced via a MAP kinase pathway, may serve as an important mediator of PDL immunoregulation involved in bone remodeling during orthodontic tooth movement.
Subject(s)
Dexamethasone/pharmacology , Extracellular Signal-Regulated MAP Kinases/physiology , Interleukin-8/biosynthesis , Interleukin-8/genetics , Periodontal Ligament/enzymology , Tumor Necrosis Factor-alpha/physiology , p38 Mitogen-Activated Protein Kinases/physiology , Anti-Inflammatory Agents/pharmacology , Bone Remodeling/physiology , Cells, Cultured , Humans , Intercellular Adhesion Molecule-1/biosynthesis , Intercellular Adhesion Molecule-1/genetics , Orthodontics, Corrective , Periodontal Ligament/cytology , Periodontal Ligament/drug effects , Signal Transduction/physiology , Tooth Migration/metabolismABSTRACT
Essential fatty acids (EFAs) play a significant role in bone metabolism. Herein we studied the adaptation of alveolar bone to physiologic tooth drift in young rats deprived of essential fatty acids from birth. Reductions in femur size and trabecular bone volume reflected body growth impairment. Along the alveolar wall, osteoclastic resorption and bone formation were depressed, disrupting the adaptive deformation of the tooth socket to ongoing migration. As a result, the periodontal ligament narrowed considerably, and further adaptation was achieved through root resorption. Essential fatty acid deficiency (EFAD), did not affect precursor recruitment or differentiation in the periodontal ligament (PDL), but caused redistribution of nonspecific-esterase (NSE)-positive osteoclast precursors and tartrate-resistant acid phosphatase (TRAP)-positive pre-osteoclasts between the bone compartment (which was depleted) and the root compartment (which was enriched). EFAD had also a marked effect on the PDL vasculature; the number of vessels was reduced, whereas their size was markedly increased. As a whole, our results show that EFAD disturbs alveolar bone adaptation to drift, but that a reaction (detrimental to root integrity) prevents root collision with the bone surface, thereby preserving the PDL as a source of precursor cells for bone and cementum homeostasis. Moreover, our results confirm that although alveolar bone resorption is arachidonic acid-dependent, the factors activating root resorption are different.
Subject(s)
Bone Remodeling/physiology , Fatty Acids, Essential/deficiency , Periodontal Ligament/pathology , Tooth Migration/metabolism , Animals , Jaw/metabolism , Jaw/pathology , Male , Osteoclasts/cytology , Periodontal Ligament/blood supply , Periodontal Ligament/cytology , Rats , Root Resorption/etiology , Root Resorption/pathology , Stem Cells/cytology , Tooth Root/metabolism , Tooth Root/pathologyABSTRACT
Localization of chondroitin sulphates in periodontal ligaments (PDL) of rat molar roots during physiological and experimental tooth movement were analysed immunohistochemically with the use of monoclonal antibodies, 3B3 and 2B6, specific to chondroitin 6-sulphate (CH-6S) and chondroitin 4-sulphate/dermatan sulfate (CH-4S/DS), respectively. The maxillary first molars of experimental animals were forced to move laterally with a 10 g weight by U-shaped wires for 3 and 7 d. In control animals, 3B3 epitope was seen in the PDL near to the bone surface facing the distal half of roots, which corresponded to the compressive side during physiological tooth movement. Immunoreactivity for 2B6 was weak or negative in the PDL. Both epitopes were present at osteoid, precementum, lacunae and canaliculli of osteocytes and cementocytes. In 3-d-treated animals, the early stage of hyalinization characterized with visible cells and fibres was observed in the PDL at the buccal side of the mesial root, which showed intense immunoreactivity for 3B3. Further 3B3 positive area seen in control animals changed its position from the distal to the buccal side of the PDL. Immunoreactivity for 2B6 did not change in the PDL of 3-d-treated animals. In 7-d-treated animals, the typical hyalinization characterized with no visible cells and fibres was seen in the PDL at the buccal sides of both mesial and disto-buccal roots, where both epitopes were present at the peripheral part of the tissue. Observation of serial sections suggested that the 3B3-positive area was present at the peripheral part of the 2B6-positive area. The present results suggest that the expression of CH-6S is related to the compressive force in non-hyalinized and hyalinized PDL, whereas that of CH-4S/DS is not influenced by the mechanical stress.