ADAMTSL1 and mandibular prognathism.

Mandibular prognathism is characterized by a prognathic or prominent mandible. The objective of this study was to find the gene responsible for mandibular prognathism. Whole exome sequencing analysis of a Thai family (family 1) identified the ADAMTSL1 c.176C>A variant as the potential defect. We cross-checked our exome data of 215 people for rare variants in ADAMTSL1 and found that the c.670C>G variant was associated with mandibular prognathism in families 2 and 4. Mutation analysis of ADAMTSL1 in 79 unrelated patients revealed the c.670C>G variant was also found in family 3. We hypothesize that mutations in ADAMTSL1 cause failure to cleave aggrecan in the condylar cartilage, and that leads to overgrowth of the mandible. Adamtsl1 is strongly expressed in the condensed mesenchymal cells of the mouse condyle, but not at the cartilage of the long bones. This explains why the patients with ADAMTSL1 mutations had abnormal mandibles but normal long bones. This is the first report that mutations in ADAMTSL1 are responsible for the pathogenesis of mandibular prognathism.

Quantitative evaluation of palatal bone thickness in patients with normal and open vertical skeletal configurations using cone-beam computed tomography.

PURPOSE: To perform a comparative analysis of the palatal bone thickness in Thai patients exhibiting class I malocclusion according to whether they exhibited a normal or open vertical skeletal configuration using cone-beam computed tomography (CBCT). MATERIALS AND METHODS: Thirty CBCT images of Thai orthodontic patients (15-30 years of age) exhibiting class I malocclusion with a normal or open vertical skeletal configuration were selected. Palatal bone thickness was measured in a 3.0-mm grid pattern on both the right and left sides. The palatal bone thickness of the normal-bite and open-bite groups was compared using the independent t-test. The level of significance was established at P<.05. RESULTS: The palatal bone thickness in the normal-bite group ranged from 2.2±1.0 mm to 12.6±4.1 mm. The palatal bone thickness in the open-bite group ranged from 1.9±1.1 mm to 13.2±2.3 mm. The palatal bone thickness was lower at almost all sites in patients with open bite than in those with normal bite. Significant differences were found at almost all anteroposterior sites along the 3 most medial sections (3.0, 6.0, and 9.0 mm lateral to the midsagittal plane) (P<.05). CONCLUSION: Class I malocclusion with open vertical skeletal configuration may affect palatal bone thickness, so the placement of temporary anchorage devices or miniscrew implants in the palatal area in such patients should be performed with caution.

Effect of compressive force on human osteoblast-like cells and bone remodelling: an in vitro study.

OBJECTIVE: The aim of this study was to determine the effect of continuous compressive force (CF) on expression by human alveolar bone-derived osteoblasts (HOBs) of some specific molecules involved in bone remodelling. DESIGN: HOBs were cultured with or without CF (control, 2.0, 4.0gcm(-2)) for 1, 3 and 7 days. Expression of alkaline phosphatase (ALP), type I collagen (Col I), osteopontin (OPN), osteocalcin (OCN), transcription factor Runx2, receptor activator of nuclear factor κB ligand (RANKL), osteoprotegerin (OPG) and prostaglandin E2 (PGE2) was analysed by real-time-polymerase chain reaction (RT-PCR), enzyme-linked immunosorbent assay (ELISA) and/or immunostaining. RESULTS: The results revealed that CF upregulated ALP and Col I expression at both messenger RNA (mRNA) and protein levels but did not affect expression of OPN and OCN mRNA. Runx2 mRNA was inhibited by CF, which also altered the expression of molecules involved in osteoclastogenesis, by enhancing RANKL expression and suppressing OPG expression. At 4.0gcm(-2) of CF, the expression of RANKL and PGE2 was significantly upregulated. CONCLUSION: The results suggest that initial application of CF on HOBs can simultaneously affect expression of markers related to both osteogenesis and osteoclastogenesis.

Initial responses of osteoblasts derived from human alveolar bone to various compressive forces.

Mechanical stress generated by orthodontic force is recognized as a major factor in the modulation of alveolar bone remodeling. During this process, osteoblasts play a crucial role, not only by participating in bone formation but also by promoting osteoclastogenesis. The aim of this study was to investigate how continuous compressive force (CF) affects human primary osteoblasts (HOBs) in terms of cell proliferation, apoptosis, and expression of interleukin-6 (IL-6) and chemokine CXC ligand 8 (CXCL8). Human primary osteoblasts, isolated from human mandibular bone pieces, were cultured with or without CF (1-4 g cm(-2)) for up to 72 h. Cell viability and proliferation were evaluated using the MTT assay. RT-PCR was used to determine the levels of expression of KI67 (a proliferation marker), BAX (a pro-apoptotic marker), BCL2 (an apoptotic inhibitor), IL6, and CXCL8 mRNAs, while a multiplexed bead immunoassay was used to measure the release of IL-6 and CXCL8. The results revealed that CF decreased cell viability and proliferation in a time- and force-dependent manner. After applying CF for 24 h, the mRNA expression of KI67 was markedly inhibited, whereas the mRNA expression of BAX and BCL2 was unaltered. In addition, CF enhanced the levels of IL6 and CXCL8 mRNAs in a force-dependent manner, whereas the levels of the corresponding proteins were reduced in the compressed HOBs.

Experimental orthodontic tooth movement and extensive root resorption: periodontal and pulpal changes.

Previous studies have reported changes both in dental pulp and in periodontal ligament (PDL) following orthodontic tooth movement. However, pulpal changes following extensive root resorption after orthodontic tooth movement have not been studied in detail. The aim of this study was therefore to evaluate inflammatory changes, both in the dental pulp and in the compressed PDL, after experimentally induced extensive root resorption. Extensive root resorption was induced in rats by the activation and re-activation of orthodontic force, with a short intervening period of no force application. The distribution of immune cells, nerve fibres and blood vessels was studied immunohistochemically using antibodies against CD68-immunoreactive (IR) cells, major histocompatibility complex (MHC) class II Ia-expressing cells, CD43-IR cells, protein gene product 9.5 (PGP 9.5), and laminin. In the compressed PDL of experimental first molars, significantly increased density of CD68-IR cells and MHC class II Ia-expressing cells were found, whereas the density of CD43-IR cells were unchanged when compared with control second molars. In the compressed PDL, there was an increased density of blood vessels, but no sprouting of nerve fibres. In the dental pulp, however, no increased density of immune cells or sprouting of nerve fibres was recorded. In conclusion, inflammation after extensive root resorption was confined to the compressed PDL, whereas the dental pulp was unaffected.