CCR5-CCL Axis in PDL during Orthodontic Biophysical Force Application.

Tooth movement by application of orthodontic biophysical force primarily reflects the role of soluble molecules released from the periodontal ligament (PDL). Thus far, many factors have been reported to be involved in orthodontic tooth movement (OTM), but key molecules that orchestrate responses of periodontal tissues to biophysical force are still enigmatic. In this in vivo study, in which the upper first molars in rats were moved, differential display-polymerase chain reaction revealed that CC chemokine receptor 5 (CCR5) level was differentially increased during OTM. Strong immunoreactivity for CCR5 was found in the PDL undergoing force application. Moreover, the in vitro compression or tension force application to primary cultured human PDL cells increased the expression of CCR5 and CCR5 ligands. In vitro tension force on human PDL cells did not induce RANKL, an osteoclastogenesis-inducing factor, but did induce the upregulation of IL12, an osteoclast inhibitory factor, and osteoblast differentiation factors, including Runx2, which was attenuated under tension by CCR5 gene silencing whereas augmented with CCR5 ligands. In contrast, in vitro compression force did not induce the expression of osteoprotegerin, a decoy receptor for RANKL and Runx2, but did induce the upregulation of RANKL, which was attenuated under compression by CCR5 gene silencing. These results suggest that the CCR5-CCR5 ligands axis in PDL cells may play a crucial role in the remodeling of periodontal tissues and can be a therapeutic target for achieving efficient OTM.

Upregulation of relaxin receptors in the PDL by biophysical force.

OBJECTIVES: We have previously reported that relaxin (Rln) expression from the ovary is upregulated by orthodontic tooth movement. This study was performed to test the hypothesis that Rln family peptides (Rxfps), the G-protein-coupled Rln receptor, is induced in periodontal ligament (PDL) cells to modulate the molecules involved in periodontal tissue remodeling while applying biophysical force. MATERIALS AND METHODS: Rats were implanted with orthodontic appliances to investigate changes to Rxfps in vivo. An in vitro biophysical force analysis was performed to measure the level of Rxfp 1 messenger RNA (mRNA) in primary human PDL cells. RESULTS: The levels of Rxfp 2 transcription and translation increased in a time-dependent manner during tooth movement. Rxfp 2 was localized in the PDL by immunofluorescence. In vitro analyses revealed that the level of Rxfp 1 mRNA in PDL cells increased significantly with both compression and tension force. The levels of matrix metalloproteinase (MMP)-1, MMP-2, interleukin-6, and vascular endothelial growth factor mRNA, which are important for periodontal tissue remodeling, also changed under force application and Rln treatment. CONCLUSIONS: PDL cells responded to Rln to modulate effector molecules for periodontal tissue remodeling by upregulating Rxfps expression under a biophysical force. CLINICAL RELEVANCE: Rln and Rxfps may serve as a PDL turnover molecule complex to control orthodontic tooth movement.

Osteoprotegerin expressed by osteoclasts: an autoregulator of osteoclastogenesis.

Osteoprotegerin (OPG) is secreted by stromal and osteoblastic lineage cells and inhibits osteoclastogenesis by preventing the interaction of receptor activator of nuclear factor-κB ligand (RANKL) with receptor activator of nuclear factor-κB (RANK). In this study, the expression of OPG in osteoclasts themselves and its biological functions during osteoclastogenesis were investigated for the first time. OPG expression in vivo in the developing rat maxilla was examined by immunofluorescence analysis. OPG expression in osteoclasts during in vitro osteoclastogenesis was determined by reverse-transcription polymerase chain-reaction (RT-PCR), Western blot, and immunofluorescence staining. We determined the function of OPG produced by osteoclasts during osteoclastogenesis by silencing the OPG gene. The effects of OPG on bone-resorbing activity and apoptosis of mature osteoclasts were examined by the assay of resorptive pit formation on calcium-phosphate-coated plate and terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling (TUNEL) staining, respectively. In the immunofluorescence findings, strong immunoreactivities were unexpectedly seen in multinucleated tartrate-resistant acid phosphatase (TRAP)-positive osteoclasts around the growing and erupting tooth germs in the rat alveolar bone. In vitro, OPG expression was significantly increased during the differentiation of osteoclasts from mouse bone-marrow-derived cells treated with a combination of macrophage colony-stimulating factor (M-CSF) and RANKL. Interestingly, it was found that OPG small interfering (si)RNA treatment during osteoclastogenesis enhanced the sizes of osteoclasts, but attenuated their bone-resorbing activity. Also, the increased chromosomal DNA fragmentation and caspase-3 activity in the late phase of osteoclastogenesis were found to be decreased by treatment with OPG siRNA. Furthermore, effects of OPG siRNA treatment on osteoclastogenesis and bone-resorbing activity were recovered by the treatment of exogenous OPG. These results suggest that OPG, expressed by the osteoclasts themselves, may play an auto-regulatory role in the late phase of osteoclastogenesis through the induction of apoptosis.

A false presence of bifid mandibular canals in panoramic radiographs.

OBJECTIVES: This study was performed in order to verify bifid mandibular canals revealed from panoramic radiographic results. METHODS: 1000 panoramic radiographs from dental patients and the panorama, cone beam CT (CBCT) and micro-CT from 40 dry mandibles were examined for bifid mandibular canals. The results were confirmed by a stereoscopic and histological examination of the cross-sectioned mandibles. RESULTS: The prevalence of bifid canals detected from the panoramic radiographs was 0.038. The panoramic radiographs from one dry mandible showed two separate radiolucent mandibular canal-like structures delineated by radio-opaque lines. However, a stereoscopic and histological examination of a cross-section of the mandible showed that only one canal was a true canal containing neurovascular bundles: the other was false, reflecting merely a bony trabecular pattern. CONCLUSIONS: The presence of bifid mandibular canals determined by panoramic radiography should be judged with great caution in relation to dental surgery.

Psychiatric morbidity of second and third grade primary school children in Korea.

This study was undertaken to identify psychiatric morbidity among Korean second and third elementary school children using an objective diagnostic interview tool. Data from 5,118 (2,723 boys, 2,395 girls; mean age = 8.41 years (SD = 0.66)) second and third grade schoolchildren were drawn from 28 elementary schools. After initial screening assessments using the 28-item Child Problem-Behavior Screening Test for parents, 672 primary caregivers were subjected to secondary screening using the Korean version of the CBCL. Two hundred and seventy-one high-risk children selected according to the K-CBCL results, 138 (50.9%) children and their primary caregivers were interviewed using the Korean version of K-SADS-PL for objective DSM-IV psychiatric diagnoses. Sixty-four (46.4%) of the hundred and thirty eight children were determined to have at least one psychiatric disorder. More boys were diagnosed as psychiatric patients than girls (46 males, 18 females; OR = 2.21). The most frequently diagnosed disorder was ADHD (46/64; 71.9%), followed by tic disorder, anxiety disorders, mental retardation, oppositional defiant disorder, and separation anxiety disorder. Two or more comorbid psychiatric disorders were found in 22 (34.4%) of the 64 patients. The computed crude percentage of psychiatric patients in this study was 4.12%, which is similar to previously published data.