osteoprotegerin and Malocclusion

To investigate the effects of different orthodontic treatments on gingival crevicular fluid chemokine CX3CL1, nuclear factor κB receptor activating factor ligand/osteoprotegerin(RANKL/OPG) levels in patients with malocclusion.. Ninety-six patients with malocclusion who were scheduled to undergo orthodontic treatment were randomly divided into four groups. All patients were treated with square wire appliance, and 0, 50, 150, 250 g of far-distal orthodontic force were given respectively. The levels of CX3CL1 and RANKL/OPG in gingival crevicular fluid were detected in four groups after 1, 2, 3, and 4 weeks of treatment. SPSS 25.0 software package was used for statistical analysis of the date.. The levels of CX3CL1, RANKL and RANKL/OPG in the gingival crevicular fluid of the four groups were continuously increased after treatment for 1-3 weeks, and decreased after 4 weeks of treatment (P<0.05). The OPG in the gingival crevicular fluid was at a low level after 1-3 weeks of treatment. There was an increase after 4 weeks of treatment (P<0.05). The levels of CX3CL1, RANKL, OPG and RANKL/OPG in gingival crevicular fluid increased gradually in group A, B, C and D (P<0.05), and the differences between the groups were statistically significant (P<0.05).. The levels of CX3CL1 and RANKL/OPG in gingival crevicular fluid are closely related to orthodontic force and treatment time, and can be used as an index to evaluate orthodontic treatment of alveolar bone remodeling.

Topics: Bone Remodeling; Chemokine CX3CL1; Gingival Crevicular Fluid; Humans; Malocclusion; Osteoprotegerin; RANK Ligand; Sputum

To determine whether mandibular condylar cartilage degradation induced by experimentally abnormal occlusion could be ameliorated via systemic administration of strontium or NBD peptide.. Six-week-old female C57BL/6J mice were used. From the seventh day after mock operation or unilateral anterior crossbite (UAC) treatment, the control and UAC mice were further respectively pharmacologically treated for 2 weeks or 4 weeks of saline (CON + Saline and UAC + Saline groups), SrCl2 (CON + SrCl2 and UAC + SrCl2 groups) or NBD peptide (CON + NBD peptide and UAC + NBD peptide groups). Changes in condylar cartilage and subchondral bone were assessed 21 and 35 days after mock operation or UAC procedure by histology and micro-CT. Real-time PCR and/or immunohistochemistry (IHC) were performed to evaluate changes in expression levels of col2a1, aggrecan, ADAMTS-5, tnf-α, il-1β, nfkbia, nuclear factor-kappaB phospho-p65 in condylar cartilage, and rankl/rank/opg in both condylar cartilage and subchondral bone.. Cartilage degradation with decreased col2a1 and aggrecan expression, and increased ADAMTS-5, tnf-α/il1-β, nfkbia and NF-κB phospho-p65 was observed in UAC + Saline groups. Subchondral bone loss with increased osteoclast numbers and decreased opg/rankl ratio was found in UAC + Saline groups compared to age-match CON + Saline groups. Cartilage degradation and subchondral bone loss were reversed by treatment of SrCl2 or NBD peptide while the same dosage in control mice induced few changes in condylar cartilage and subchondral bone.. The results demonstrate reverse effect of systemic administration of strontium or NBD peptide on UAC-induced condylar cartilage degradation and subchondral bone loss.

Topics: ADAM Proteins; ADAMTS5 Protein; Aggrecans; Animals; Cartilage, Articular; Collagen Type II; Dental Occlusion; Female; I-kappa B Proteins; Immunohistochemistry; Interleukin-1beta; Malocclusion; Mandibular Condyle; Mice; Mice, Inbred C57BL; NF-KappaB Inhibitor alpha; Osteoclasts; Osteoprotegerin; Peptides; Proteoglycans; RANK Ligand; Real-Time Polymerase Chain Reaction; Receptor Activator of Nuclear Factor-kappa B; RNA, Messenger; Strontium; Transcription Factor RelA; Tumor Necrosis Factor-alpha

Degenerative changes of condylar subchondral bone occur frequently in temporomandibular disorders. Although psychologic stresses and occlusal abnormalities have been implicated in temporomandibular disorder, it is not known if these risks represent synergistic comorbid factors that are involved in condylar subchondral bone degradation that is regulated by the sympathetic nervous system. In the present study, chronic immobilization stress (CIS), chemical sympathectomy, and unilateral anterior crossbite (UAC) were sequentially applied in a murine model. Norepinephrine contents in the subjects' serum and condylar subchondral bone were detected by ELISA; bone and cartilage remodeling parameters and related gene expression in the subchondral bone were examined. Subchondral bone loss and increased subchondral bone norepinephrine level were observed in the CIS and UAC groups. These groups exhibited decreased bone mineral density, volume fraction, and bone formation rate; decreased expressions of osterix, collagen I, and osteocalcin; but increased trabecular separation, osteoclast number and surface, and RANKL expression. Combined CIS + UAC produced more severe subchondral bone loss, higher bone norepinephrine level, and decreased chondrocyte density and cartilage thickness when compared to CIS or UAC alone. Sympathectomy simultaneously prevented subchondral bone loss and decreased bone norepinephrine level in all experimental subgroups when compared to the vehicle-treated counterparts. Norepinephrine also decreased mRNA expression of osterix, collagen I, and osteocalcin by mesenchymal stem cells at 7 and 14 d of stimulation and increased the expression of RANKL and RANKL/OPG ratio by mesenchymal stem cells at 2 h. In conclusion, CIS and UAC synergistically promote condylar subchondral bone loss and cartilage degradation; such processes are partially regulated by norepinephrine within subchondral bone.

Topics: Animals; Bone Density; Bone Resorption; Cartilage, Articular; Cell Count; Cell Culture Techniques; Chondrocytes; Collagen Type I; Disease Models, Animal; Female; Immobilization; Malocclusion; Mandibular Condyle; Mesenchymal Stem Cells; Mice; Mice, Inbred C57BL; Norepinephrine; Osteocalcin; Osteoclasts; Osteogenesis; Osteoprotegerin; RANK Ligand; Risk Factors; Stress, Psychological; Sympathectomy, Chemical; Temporomandibular Joint Disorders; Transcription Factors

Dietary loading has been reported to have an effect on temporomandibular joint (TMJ) remodeling via periodontal-muscular reflex. We therefore examined whether reducing dietary loading decreased TMJ degradation induced by the unilateral anterior crossbite prosthesis as we recently reported.. Forty 6-week-old female C57BL/6J mice were randomly divided into two experimental and two control groups. One experimental and one control group received small-size diet and the other two groups received large-size diet. Unilateral anterior crossbite prosthesis was created in the two experimental groups. The TMJ samples were collected 3 weeks after experimental operation. Histological changes in condylar cartilage and subchondral bone were assessed by Hematoxylin & Eosin, toluidine blue, Safranin O and tartrate-resistant acid phosphatase staining. Real-time polymerase chain reaction (PCR) and/or immunohistochemistry were performed to evaluate the expression levels of Collagen II, Aggrecan, a disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5) and RANKL/RANK/OPG in TMJ condylar cartilage and/or subchondral bone.. Thinner and degraded cartilage, reduced cartilage cellular density, decreased expression levels of Collagen II and Aggrecan, loss of subchondral bone and enhanced osteoclast activity were observed in TMJs of both experimental groups. However, the cartilage degradation phenotype was less severe and cartilage ADAMTS-5 mRNA was lower while OPG/RANKL ratio in cartilage and subchondral bone was higher in the small-size than large-size diet experimental group. No differences of histomorphology and the tested molecules were found between the two control groups.. The current findings suggest that a lower level of functional loading by providing small-size diet could reduce TMJ degradation induced by the biomechanical stimulation from abnormal occlusion.

Topics: ADAM Proteins; ADAMTS5 Protein; Aggrecans; Animals; Body Weight; Cartilage, Articular; Collagen Type II; Dental Prosthesis; Diet; Disease Progression; Female; Malocclusion; Mandibular Condyle; Mastication; Mice; Mice, Inbred C57BL; Osteoarthritis; Osteoclasts; Osteoprotegerin; RANK Ligand; Temporomandibular Joint Disorders

The purposes of this research were to investigate the long-term responses of mandibular condylar cartilage to experimentally induced disordered occlusion and to evaluate changes in the expression of the SDF-1/CXCR4 axis.. Experimentally induced disordered occlusions were created in 8-week-old female Sprague-Dawley rats by orthodontic methods. After 24 weeks, remodeling of the mandibular condylar cartilage was assessed by hematoxylin and eosin staining. Protein and mRNA expression of SDF-1, CXCR4, MMP9, IL6, OPG, and RANKL were investigated by means of immunohistochemical staining and real-time polymerase chain reaction.. Obvious cartilage degenerative remodeling responses were observed; they appeared as uneven distributions of cellular disposition, loss of cartilage surface integrity, and cell-free areas. Regenerative responses presenting as thickening of the whole and the calcified cartilage layers in the experimental group were also observed. Compared with the age-matched controls, the protein and mRNA levels of SDF-1, CXCR4, MMP9, IL6, and OPG, but not RANKL, were increased in the experimental group (all, P <0.05). In addition, the mRNA level of RANKL/OPG showed a decreasing trend in the experimental group compared with the age-matched controls (P = 0.052).. This study demonstrated that long-term experimentally induced disordered occlusion leads to a combined response in degeneration and regeneration of mandibular cartilage, accompanied by active interaction of the SDF-1/CXCR4 axis and local upregulation of MMP9, IL6, and OPG.

Topics: Animals; Bone Remodeling; Cartilage, Articular; Chemokine CXCL12; Female; Interleukin-6; Malocclusion; Mandibular Condyle; Matrix Metalloproteinase 9; Osteoarthritis; Osteoprotegerin; RANK Ligand; Rats; Rats, Sprague-Dawley; Receptors, CXCR4; Regeneration; Temporomandibular Joint Disorders

External apical root resorption (EARR) is a common orthodontic treatment sequela. Previous studies implicate a substantial genetic component for EARR. Using a candidate gene approach, we investigated possible linkage of EARR associated with orthodontic treatment with the TNSALP, TNFalpha, and TNFRSF11A gene loci. The sample was comprised of 38 American Caucasian families with a total of 79 siblings who completed comprehensive orthodontic treatment. EARR was assessed by means of pre- and post-treatment radiographs. Buccal swab cells were collected for extraction and analysis of DNA. No evidence of linkage was found with EARR and the TNFalpha and TNSALP genes. Non-parametric sibling pair linkage analysis identified evidence of linkage (LOD = 2.5; p = 0.02) of EARR affecting the maxillary central incisor with the microsatellite marker D18S64 (tightly linked to TNFRSF11A). This indicates that the TNFRSF11A locus, or another tightly linked gene, is associated with EARR.

Topics: Child; Chromosomes, Human, Pair 18; Female; Genetic Linkage; Genetic Markers; Genetic Predisposition to Disease; Glycoproteins; Humans; Male; Malocclusion; Microsatellite Repeats; Orthodontics, Corrective; Osteoprotegerin; Pedigree; Polymorphism, Genetic; Receptors, Cytoplasmic and Nuclear; Receptors, Tumor Necrosis Factor; Root Resorption; Siblings; Statistics, Nonparametric