osteoprotegerin and Tooth-Mobility

Orthodontic anchorage is one of the most challenging aspects of Orthodontics. Preventing undesired movement of teeth could result in safer and less complicated orthodontic treatment. Recently, several reviews have been published about the effects of different molecules on bone physiology and the clinical side effects in Orthodontics. However, the effects of local application of these substances on the rate of orthodontic tooth movement have not been assessed.. The aim of this research was to analyze the scientific evidence published in the literature about the effects of different molecules on orthodontic anchorage.. The literature was systematically reviewed using PubMed/Medline, Scopus and Cochrane databases from 2000 up to July 31st, 2014. Articles were independently selected by two different researchers based on previously established inclusion and exclusion criteria, with a concordance Kappa index of 0.86. The methodological quality of the reviewed papers was performed.. Search strategy identified 270 articles. Twenty-five of them were selected after application of inclusion/exclusion criteria, and only 11 qualified for final analysis. Molecules involved in orthodontic anchorage were divided into three main groups: osteoprotegerin (OPG), bisphosphonates (BPs) and other molecules (OMs).. Different drugs are able to alter the bone remodeling cycle, influencing osteoclast function and, therefore, tooth movement. Thus, they could be used in order to provide maximal anchorage while preventing undesired movements. OPG was found the most effective molecule in blocking the action of osteoclasts, thereby reducing undesired movements.

Topics: Acetylcysteine; Animals; Anti-Inflammatory Agents; Antioxidants; Bone Remodeling; Celecoxib; Clodronic Acid; Diclofenac; Diphosphonates; Humans; Imidazoles; Interferon-gamma; Isoxazoles; Lactones; Mice; Orthodontic Anchorage Procedures; Osteoclasts; Osteoprotegerin; Pamidronate; Rats; Resveratrol; Stilbenes; Sulfones; Tooth Mobility; Tooth Movement Techniques; Zoledronic Acid

To measure the changes in tooth mobility, alveolar bone, and receptor activator of nuclear factor kappa-B ligand (RANKL)/osteoprotegerin (OPG) in the gingival crevicular fluid (GCF) during orthodontic treatment to regain incisal function in the presence and absence of biting exercises.. Thirty-six females (42.3 ± 6.5 years old) with periodontally compromised upper incisors received orthodontic treatment to obtain ideal incisor relationships. Eighteen subjects in the experimental biting exercise group were instructed to bite a soft plastic roll for 5 min/d; the 18 control subjects were not given plastic rolls. Alveolar bone thickness, height, and density around the upper incisors were assessed at three root levels using cone-beam computed tomography. GCF was collected at the labial and palatal sites of the upper incisors at pretreatment (T0), end of treatment (T1), 1 month after T1 (T2), and 7 months after T1 (T3). RANKL/OPG was determined using enzyme-linked immunosorbent assays.. Labial and palatal bone thickness significantly increased (>twofold) from T1 to T3 in the experimental group at all three root levels (all P < .05). Bone thickness correlated negatively with RANKL/OPG ratio between T1 and T2 ( P < .05). Tooth mobility, bone height, and density were not significantly different between T1 and T3.. Biting exercises significantly increased bone thickness but did not affect tooth mobility, bone height, or density. The RANKL/OPG ratio decreased 1 month after treatment (T2) and correlated with increased bone thickness. ( ClinicalTrials.in.th TCTR20170625001).

Topics: Adult; Alveolar Bone Loss; Cone-Beam Computed Tomography; Exercise Therapy; Female; Gingival Crevicular Fluid; Humans; Incisor; Maxilla; Osteoprotegerin; Periodontitis; RANK Ligand; Tooth Mobility; Treatment Outcome

Orthodontic tooth movement (OTM) is a specific treatment of malocclusion, whose regulation mechanism is still not clear. This study aimed to reveal the relationship between the sympathetic nervous system (SNS) and OTM through the construction of an OTM rat model through the utilization of orthodontic nickeltitanium coiled springs. The results indicated that the stimulation of SNS by dopamine significantly promote the OTM process represented by the much larger distance between the first and second molar compared with mere exertion of orthodontic force. Superior cervical ganglionectomy (SCGx) can alleviate this promotion effect, further proving the role of SNS in the process of OTM. Subsequently, the ability of orthodontic force to stimulate the center of the SNS was visualized by the tyrosin hydroxylase (TH) staining of neurons in ventromedial hypothalamic nucleus (VMH) and arcuate nucleus (ARC) of the hypothalamus, as well as the up-regulated expression of norepinephrine in local alveolar bone. Moreover, we also elucidated that the stimulation of SNS can promote osteoclast differentiation in periodontal ligament cells (PDLCs) and bone marrow-derived cells (BMCs) through regulation of receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG) system, thus promoting the OTM process. In conclusion, this study provided the first evidence for the involvement of the hypothalamus in the promotion effect of SNS on OTM. This work could provide a novel theoretical and experimental basis for further understanding of the molecular mechanism of OTM.

Topics: Alveolar Process; Animals; Cells, Cultured; Dopamine; Ganglionectomy; Male; Mechanotransduction, Cellular; Norepinephrine; Osteoclasts; Osteogenesis; Osteoprotegerin; Periodontal Ligament; RANK Ligand; Rats, Sprague-Dawley; Superior Cervical Ganglion; Tooth Migration; Tooth Mobility; Tooth Movement Techniques; Ventromedial Hypothalamic Nucleus

Tooth movement is a biological process of bone remodeling induced by mechanical force. Sclerostin secreted by osteocytes is mechanosensory and important in bone remodeling. However, little is known regarding the role of sclerostin in tooth movement. In this study, models of experimental tooth movement were established in rats and mice. Sclerostin expression was investigated with immunohistochemistry staining, and osteoclastic activity was analyzed with tartrate-resistant acid phosphatase (TRAP) staining. MLO-Y4 osteocyte-like cells underwent uniaxial compression and tension stress or were cultured in hypoxia conditions. Expression of sclerostin was assessed by RT-qPCR and ELISA. MLO-Y4 cells were cultured with recombinant human sclerostin (rhSCL) interference and then co-cultured with RAW264.7 osteoclast precursor cells. Expressions of RANKL and OPG were analyzed by RT-qPCR, and osteoclastic activity was assessed by TRAP staining. During tooth movement, sclerostin was expressed differently in compression and tension sites. In SOST knock-out mice, there were significantly fewer TRAP-positive cells than in WT mice during tooth movement in compression sites. In-vitro studies showed that the expression of sclerostin in MLO-Y4 osteocyte-like cells was not different under a uniaxial compression and tension force, whereas hypoxia conditions significantly increased sclerostin expression in MLO-Y4 cells. rhSCL interference increased the expression of RANKL and the RANKL/OPG ratio in MLO-Y4 cells and the osteoclastic induction ability of MLO-Y4 cells in experimental osteocyte-osteoclast co-culture. These data suggest that sclerostin plays an important role in the bone remodeling of tooth movement.

Topics: Adaptor Proteins, Signal Transducing; Animals; Bone Morphogenetic Proteins; Bone Remodeling; Cell Hypoxia; Cell Line; Genetic Markers; Glycoproteins; Humans; Intercellular Signaling Peptides and Proteins; Male; Mice; Osteocytes; Osteoprotegerin; RANK Ligand; Rats; Rats, Sprague-Dawley; RAW 264.7 Cells; Tartrate-Resistant Acid Phosphatase; Tooth Mobility; Tooth Movement Techniques

The statin class of drugs enhances osteogenesis and suppresses bone resorption, which could be a plausible biologic mechanism for mitigation of orthodontic relapse. We aimed to determine whether atorvastatin (ATV) might affect orthodontic relapse and osteoclastogenesis by modulating expression of RANKL and osteoprotegerin (OPG), crucial molecules involved in bone turnover. Furthermore, we analyzed the adverse effects of ATV on femur turnover and endochondral ossification.. Wistar rats were subjected to orthodontic tooth movement for 21 days, followed by removal of the appliance and ATV or saline solution administration. Up to 7, 14, and 21 days of ATV administration, tooth relapse was measured, and maxilla and femur sections were obtained and prepared for hematoxylin and eosin, TRAP, and immunohistochemical (RANKL and OPG) staining.. ATV decreased tooth relapse (P = 0.03) and osteoclast counts (P = 0.04), which were positively correlated (P = 0.006). Statin administration increased periodontal expression of OPG (P = 0.008), but not of RANKL protein. ATV administration also enhanced growth plate cartilage thickness.. Statin-induced OPG overexpression reduces relapse after orthodontic tooth movement, in a phenomenon correlated with decreased osteoclast counts. This phenomenon sheds light on OPG as a molecular target that modulates maxillary bone metabolism and orthodontic relapse.

Topics: Animals; Atorvastatin; Bone Remodeling; Femur; Immunohistochemistry; Male; Maxilla; Osteoclasts; Osteoprotegerin; RANK Ligand; Rats; Rats, Wistar; Recurrence; Tooth Mobility; Tooth Movement Techniques

Anchorage is one of the most challenging sides in orthodontics. The use of biological modulators that inhibit osteoclasts could be a solution to address these problems and provide new adjunctive approaches. The aim of this study was to assess the effectiveness of recombinant osteoprotegerin fusion protein (OPG-Fc) in orthodontic anchorage.. Two groups of male Sprague-Dawley rats were utilized. The animals in the experimental group received twice-weekly injections with high dose of OPG-Fc (5.0mg/kg) in mesial and distal mucosa of the first molars, and those in the control group received no drugs. Right first maxillary molars were mesialized using a calibrated nickel-titanium spring connected to an anterior mini-screw. Tooth movement was measured by two blinded observers using scanned and magnified stone casts. Receptor activator of nuclear factor κB (RANK), run-related transcription factor 2 (Runx2), type I collagen, vimentin, matrix metalloproteinases 2 and 9, S100 protein and the putative mechanoproteins acid-sensing ion channel (ASIC2) and transient receptor potential vainilloid 4 (TRPV4) were evaluated using immunohistochemistry.. OPG-Fc group showed an important decreased in mesial molar movement with only 52%, 31%, and 22% of the total mesial molar movement compared with control group at Days 7, 14, and 21, respectively (P < 0.001). RANK ligand and Runx2 positive cells were severely reduced after OPG-Fc treatment. Periodontal ligament architecture, cell arrangement, and immunohistochemical patter for vimentin, type I collagen and the mechanoproteins TRPV4 and ASIC2 were altered by tooth movement and all these parameters altered by the applied treatment.. OPG-Fc effectively inhibits osteoclastogenesis resulting in improved bone quantity and orthodontic anchorage. Based on present results, OPG-Fc could have clinical utility in preventing undesired tooth movements.

Topics: Animals; Drug Administration Schedule; Drug Evaluation, Preclinical; Male; Maxilla; Molar; Osteoclasts; Osteogenesis; Osteoprotegerin; Periodontal Ligament; RANK Ligand; Rats, Sprague-Dawley; Recombinant Fusion Proteins; Tooth Mobility; Tooth Movement Techniques

Relapse after orthodontic tooth movement is a significant problem in orthodontics. The purpose of this study was to examine the efficacy of the osteoclast inhibitor osteoprotegerin-Fc (OPG-Fc) for inhibiting postorthodontic relapse. Rat maxillary molars were moved mesially and allowed to relapse for 24 days. Low-dose (1 mg/kg) or high-dose (5 mg/kg) OPG-Fc or saline was injected adjacent to the molars during relapse. Tooth movement, micro-CT, histologic bone quality, and serum OPG and TRAP-5b were measured. OPG-Fc injections significantly diminished postorthodontic relapse from 63% (0.78/1.20 mm) of total movement in vehicle control rats to 31% (0.31/1.00 mm) in low-dose and 24% (0.28/1.16 mm) in high-dose OPG-Fc groups 24 days after appliance removal. Normalization of bone and periodontal tissues occurred as early as 8 and 16 days in the high- and low-dose OPG-Fc-treated groups, respectively, while the vehicle-treated group showed only partial tissue recovery 24 days following tooth movement. After 24 days of relapse, there was complete recovery to pre-tooth-movement values for bone volume fraction (BVF) and tissue mineral density (TMD) in both the low- and high-dose OPG-Fc groups, while BVF recovered only partially and TMD did not recover in the vehicle control group. Greatly elevated serum OPG levels and reduced serum TRAP-5b levels in OPG-Fc-treated animals indicated systemic exposure to locally injected drug. The profound decrease in postorthodontic relapse by local OPG-Fc administration indicates that osteoclasts are critical to bone maturation following tooth movement and points to the potential pharmacologic use of OPG-Fc or other RANKL inhibitors for orthodontic retention.

Topics: Animals; Male; Osteoprotegerin; Rats; Rats, Sprague-Dawley; Recombinant Proteins; Recurrence; Tooth; Tooth Mobility; Tooth Movement Techniques