Masseter muscle is one of the major muscles of mastication, and is comprised of actin and myosin myofibrils organized into sarcomeric contractile units. Structurally, sarcomeres are repeating portions of myofibrils between neighboring Z-lines (a.k.a. Z-disc, Z-band). The Z-line or Z-disc is composed of non-contractile proteins that provide mechanical stability to the sarcomere. One of the proteins of Z-disc is alpha-B-crystallin, a protein product of the gene CRYAB. Together with several other proteins of the Z-disc, CRYAB gene has been found to be up-regulated in Actn3 knock-out mice. In addition, CRYAB is suspected to be a pain mediator gene, having similar structure and function to CRYAA (alpha,A-crystallin) identified as one of the candidate genes from the Pain Research Panel, previously investigated in the Orofacial Pain: Prospective Evaluation and Risk Assessment (OPPERA) Study. Finally, in a microarray of global gene expression CRYAB was increased in subjects with facial asymmetry. We have examined CRYAB expression in masseter muscle of 64 orthognathic surgery patients to determine associations with skeletal malocclusions. Salivary DNA was genotyped for a single nucleotide polymorphism (SNP) for ACTN3 (rs1815739) and masseter muscle RNA isolated from an orthognathic surgery patient population. These genotyping and expression data have been used to identify differences in CRYAB expression in sub-groups of our patient population with Class II and III, normal, open and deep bite malocclusions who are null for ACTN3. In addition, we evaluated expression levels of CRYAB in patients with TMD-related myalgia. We found that relative quantities of CRYAB expression differed very significantly between sexes (p=0.005). ANOVA comparison between all subjects with and without TMD-myalgia indicated that males with TMD-myalgia had significantly greater (p<0.02) expression than other groups. An unpaired t-test showed that with TMD-related myalgia, CRYAB expression was significantly higher (p=0.03) in males than in females. ANOVA comparison between sexes with Class II and Class III malocclusions showed greater expression of CRYAB (p=0.005) in males with Class II. Expression was likewise greater in males with Class III malocclusion than in females with Class III (p<0.01). Among different age groups, subjects 25 years of age or younger had significantly (p value=0.025) increased expression of CRYAB gene. There were no significant differences for genotypes or facial asymmetry. / Oral Biology

Objective: Genetic loci for ATP2A2 kinase, NUAK1, and phosphatase PPP1CC are associated with skeletal muscle strength phenotypes. ATP2A2 is a calcium ion transport ATPase in sarcoplasmic reticulum that is predominantly expressed in cardiac and slow-twitch fibers. NUAK1, an AMP-activated protein kinase, and PPP1CC, a subunit of protein phosphatase 1, are involved in glycogen metabolism during skeletal muscle contraction. The aim of this study is to investigate whether these genes are associated with masseter muscle composition and function in the development of skeletal malocclusion. Methods: A total of 56 orthognathic surgery patients were classified as having skeletal Class I, Class II, or III sagittal malocclusions with normal, open, or deep bites vertically, with or without facial asymmetry. Masseter muscle samples were collected during the mandibular osteotomies, frozen, and sent to the Kornberg School of Dentistry. Tissue from eleven patients was used for gene expression analysis on Affymetrix HT2.0 microarray chips and a principle components analysis. Then, these plus an additional 45 masseter samples were used for quantitative RT-PCR. Expression data for the three genes of interest were evaluated in the microarray and corroborated and expanded upon with RT-PCR data. ANOVA and unpaired t-tests were performed to determine correlations between ATP2A2, NUAK1, and PPP1CC expression levels and vertical and sagittal malocclusion classifications. Additional ANOVA and unpaired t-tests were performed to determine correlations between ATP2A2 expression level and signs and symptoms of temporomandibular disorder (TMD) with and without pain and facial asymmetry, and relative to the expression levels of a second gene associated with muscle strength phenotypes (ACTN3). Finally, Kendall Tau analyses were performed to compare ATP2A2 expression levels in subjects grouped by malocclusion classification to masseter muscle composition, including mean fiber area (MFA) and mean percent occupancy (MPO) of each fiber type. Results: Principle component analysis revealed two patients with genetic expression levels that deviated from the group. These were the only patients diagnosed with facial asymmetry. Microarray data showed that in these patients ATP2A2 and PPP1CC were significantly decreased. NUAK1 was decreased to a lesser extent. Also, among other genes in the same functional categories, ATP2A1 expression was -30.45 fold (P<6.11X10-6) and PPP3CC expression was -2.96 fold (P<2.03X10-5) in the patients with facial asymmetry. RT-PCR results showed NUAK1 and PPP1CC were differentially expressed at lower, but not statistically significant levels in subjects with craniofacial asymmetry. However, RT-PCR did verify that ATP2A2 expression is down regulated in subjects with mild to severe forms of asymmetry as compared to subjects with facial symmetry (p=0.022). ANOVA and unpaired t-test analyses illustrated that there was no significant differences in ATP2A2 expression in patients with different vertical, saggital, or combined vertical/sagittal malocclusion diagnoses. There was a significant association between the lateral differences in ATP2A2 expression, between right- and left-sided masseter biopsies within the same individual, in subjects with Class III malocclusions with different vertical diagnoses. Here, lateral differences were greatest in open bite, intermediate in deep bite, and lowest in normal Class III subjects. Kendall tau analyses were performed to compare ATP2A2 expression levels and masseter composition (MFA/MPO of type I, hybrid, and type II fibers) in all subjects, subjects with Class II malocclusions, and subjects with Class III malocclusions. Regardless of sagittal malocclusion, all subjects showed a negative correlation with type IIA MPO that was highly significant (r=-0.46; p=0.004). Also, ATP2A2 associations in Class II subjects were positive with type I MFA (r=0.36; p=0.04) and negative with type IIA MPO (r=-0.59; p=0.001). Correlations for Class III subjects were typically negative and not significant. Also, Kendall tau correlations were performed to compare ATP2A2 expression with the composition of each fiber type in patients grouped by both sagittal and vertical malocclusion classification. These found decreased type IIA fiber MPO correlated significantly (p = 0.024) with increased relative ATP2A2 expression in subjects with Class II, normal bite malocclusions (n = 6, R2 = 0.8127). Finally, ATP2A2 expression was not associated with most phenotypic traits exhibited by the surgery subjects such as presence of signs/symptoms of TMD with and without pain and facial asymmetry. However there was an association between decreased lateral differences in ATP2A2 expression in subjects with asymmetry with the TC ACTN3 genotype as compared to subjects with the TC ACTN3 genotype and facial symmetry. Conclusions: ATP2A2 promotes calcium transport in slow twitch and cardiac muscle contraction-relaxation cycling. Decreased expression of this gene in patients with asymmetries suggests that down regulation of the calcium handling capacities of muscle fibers may influence the development of abnormal craniofacial phenotypes. Both NUAK1 and PPP1CC are thought to play metabolic regulatory or responsive roles to muscle contraction. Decreased expression of these genes may accompany alterations of fiber-type form and metabolic properties to adversely affect jaw development. Additionally, ATP2A2 correlations indicate that this calcium channel protein may be important for type I fiber function, but not type IIA in masseter muscle from Class II subjects, suggesting a functional influence on malocclusions. ATP2A2 does not appear to function differentially in fiber types that influence development of Class III malocclusion. Further studies with more subjects are needed to increase experimental power. / Oral Biology

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal.

This study aimed to examine end-of-treatment outcomes of severe Class II Division I malocclusion patients treated with surgical or non-surgical approaches. This study tests the hypotheses that occlusal outcomes (ABO-OGS) at end of treatment will be similar while cephalometric outcomes will differ between these groups. A total of 60 patients were included: 20 of which underwent surgical correction and 40 of which did not. The end of treatment ABO-OGS and cephalometric outcomes were compared by Mann-Whitney U tests and multivariable linear regression models. Following adjustment for multiple confounders (age, gender, complexity of case, and skeletal patterns), the final deband score (ABO-OGS) was similar for both groups (23.8 for surgical group versus 22.5 for non-surgical group). Those treated surgically had a significantly larger reduction in ANB angle, 3.4 degrees reduction versus 1.5 degrees reduction in the non-surgical group (p=0.002). The surgical group also showed increased maxillary incisor proclination (p=0.001) compared to candidates treated non-surgically. This might be attributed to retroclination of incisors during treatment selection in the non-surgical group – namely, extraction of premolars to mask the discrepancy. Studies such as this are necessary because they begin to give practitioners view of not only the outcomes of a single treatment plan, but a comprehensive approach by providing evidence of the over-arching treatment used for successful treatment in both groups.

Mémoire numérisé par la Division de la gestion de documents et des archives de l'Université de Montréal

Thesis (M.S.)--University of Southern California, 1996. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (M.S.)--University of Southern California, 1999. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Thesis (M.S.)--University of Southern California, 1999. / Includes bibliographical references.

Thesis (M.S.)--University of Southern California, 1996. / eContent provider-neutral record in process. Description based on print version record. Includes bibliographical references.

Orientador: Francisco Antonio Bertoz / Banca: Arnaldo Pinzan / Banca: Kurt Faltin Júnior / Banca: Marcos Rogério de Mendonça / Banca: Ricardo César Moresca / Resumo: Neste trabalho foram avaliadas as alterações esqueléticas e dentárias ocorridas após o tratamento da má-oclusão de classe II, divisão1ª, com a utilização do aparelho extrabucal com tração cervical tipo Kloehn (KHG), forças ortopédicas e expansão rápida da maxila. O tratamento foi realizado em 28 pacientes com idade cronológica entre 9 anos e 6 meses e 11 anos completos e maturação das vértebras cervicais nos estágios de iniciação (12 pacientes), aceleração (10 pacientes) ou transição (6 pacientes), os quais foram avaliados por meio de cefalometria de Ricketts em telerradiografias em norma lateral nas fases pré-tratamento (T1), pós-tratamento ou após a correção da relação molar (T2) e 12 meses pós-tratamento (T3). Após a análise estatística realizada pelo teste de Newman-Keuls para comparações múltiplas e análise de variância (P<0,05%), os resultados mostraram que não houve deslocamento posterior da maxila, mas o deslocamento anterior foi inibido. O crescimento mandibular normal e a concomitante inibição do deslocamento anterior da maxila contribuíram para a obtenção de uma relação molar de Classe I. Houve movimento distal dentoalveolar dos caninos e molares superiores. A expansão maxilar previamente à utilização do AEB com forças ortopédicas não contribuiu para o movimento posterior da maxila. O tempo médio para a correção da relação molar foi de 6 meses. / Abstract: This study evaluated the skeletal and dental changes after Class II, Division 1 malocclusion treatment with Kloehn cervical headgear (KHG), orthopedics forces and previous maxillary expansion. The sample consisted of 28 subjects, all with chronological ages between 9 years and 6 months and 11 years and Cervical Vertebral Maturation (CVM) at the stages initiation (12 subjects), acceleration (10 subjects) or transition (6 subjects). Ricketts lateral cephalograms were taken at three phases: pretreatment (T1), posttreatment or after the correction of the molar relation (T2) and 12 months posttreatment (T3). Statistical analysis was performed with the test of Newman-Keuls for multiple comparisons and analysis of variance (P<0.05%) to determine the skeletal and dental changes. Results demonstrated that the maxilla was not displaced posteriorly, but its anterior displacement was inhibited. The normal mandibular growth and the inhibition of the anterior displacement of the maxilla contributed for the achievement of the Class I molar relationship. Cuspids and upper molars dentoalveolar distal movement were found. Maxillary expansion previously to the use of KHG with orthopedics forces did not contribute for the posterior maxillary movement. The average time for molar correction was six months. / Doutor