ACTN3 genotype influences masseter muscle characteristics and self-reported bruxism.

OBJECTIVES: Main aim of the study was to explore the association between genetic polymorphisms in ACTN3 and bruxism. Secondary objectives included masseter muscle phenotypes assessment between bruxers and non-bruxers and according to genetic polymorphisms in ACTN3. MATERIALS AND METHODS: Fifty-four patients undergoing orthognathic surgery for correction of their malocclusion were enrolled. Self-reported bruxism and temporomandibular disorders status were preoperatively recorded. Saliva samples were used for ACTN3 genotyping. Masseter muscle samples were collected bilaterally at the time of orthognathic surgery to explore the muscle fiber characteristics. RESULTS: There were significant differences in genotypes for rs1815739 (R577X nonsense) (p = 0.001), rs1671064 (Q523R missense) (p = 0.005), and rs678397 (intronic variant) (p = 0.001) between bruxers and non-bruxers. Patients with self-reported bruxism presented a larger mean fiber area for types IIA (p = 0.035). The mean fiber areas in individuals with the wild-type CC genotype for rs1815739 (R577X) were significantly larger for type IIA fibers (1394.33 µm2 [572.77 µm2 ]) than in those with the TC and TT genotypes (832.61 µm2 [602.43 µm2 ] and 526.58 µm2 [432.21 µm2 ] [p = 0.014]). Similar results for Q523R missense and intronic variants. CONCLUSIONS: ACTN3 genotypes influence self-reported bruxism in patients with dentofacial deformity through specific masseter muscle fiber characteristics.

Temporomandibular Joint Dysplasia in Cranio-Maxillofacial Dysplasia: A Retrospective Study. Guideline Treatment Proposal.

INTRODUCTION: Cranio-Maxillofacial Dysplasias (CMD), including Craniofacial Microsomias, syndromes (such as Treacher Collins or Williams) and isolated Condylo-Mandibulo-Dysplasia, is a controversial subject with treatments as diverse as diagnostic classifications. The authors present here a retrospective study of 85 patients, with congenital condyle dysplasia arising from these 3 main types of CMD, treated with different techniques that aimed to normalize the facial skeleton and occlusion. METHODS: The authors studied retrospectively 85 patients, aged from 3 to 53 years old, affected by different types of CMD. Treatment options included: costochondral grafts, orthognathic surgeries, distraction osteogenesis procedures, orthodontic and dentofacial orthopedic treatments, and soft tissues surgeries. Outcomes were evaluated by the surgical team. RESULTS: Seventeen patients were treated with costochondral grafting, 14 with distraction osteogenesis, 17 with orthodontic and dentofacial orthopedic, and 45 with orthognathic surgery. The authors did not perform any nerve grafting or temporomandibular joints prosthesis placement. Fifty-one patients presented an excellent result, 10 a good result, 9 a poor result, 2 a bad result, and 14 an unknown result. DISCUSSION: Several different treatments of CMD can be proposed. The authors think that major defect in children should undergo costochondral grafting because of its growth potential while in case of minor defect, orthopedic treatment should be tried in the first place. Distraction osteogenesis should be reserved for cases with poor response after orthopedic treatment or growth insufficiency with costochondral grafting. Orthognathic surgery is often necessary at the end of the growth period to obtain an excellent result. Temporomandibular joints prosthesis should be reserved for extreme cases.

Pre-operative parafunctional or dysfunctional oral habits are associated with the temporomandibular disorders after orthognathic surgery: An observational cohort study.

BACKGROUND: Temporomandibular disorders (TMDs) are frequent and disabling, and hence, preventing them is an important health issue. Combining orthodontic and surgical treatments for malocclusions has been shown to affect temporomandibular joint (TMJ) health. However, publications regarding the risk factors that predict negative TMJ outcomes after orthognathic surgery are scarce. OBJECTIVE: Present prospective cohort study was conducted to identify an association between pre-operative dysfunctional/parafunctional oral habits and the presence of TMD symptoms after orthognathic surgery. METHOD: We included 237 patients undergoing orthodontics and surgical treatment for malocclusions associated with dentofacial deformities within the Department of Oral and Maxillofacial Surgery of the University of Lille. Their parafunctional and dysfunctional oral habits were recorded through clinical examination along with the presence of TMD symptoms before and after the surgery. According to the Research Diagnostic Criteria for Temporomandibular Disorders (RDC/TMD) classification, the TMD symptoms studied were myalgia, arthralgia, disc displacement with or without reduction. RESULTS: Multivariate analysis revealed significant associations among bruxism (odds ratio [OR] 3.17 [1.066; 9.432]), lingual interposition (OR 4.241 [1.351; 13.313]), as well as primary swallowing (OR 3.54 [1.225; 10.234]) and the presence of postoperative symptoms of myalgia. Moreover, a significant association was observed between the presence of any dysfunctional oral habit and postoperative disc displacement with reduction (OR 4.611 [1.249; 17.021]). CONCLUSION: Bruxism and dysfunctional oral habits were shown to be risk factors for the presence of TMD symptoms also after combined orthodontic and surgical treatment. Treating such habits before orthognathic surgery should help prevent TMD.

ENPP1 and ESR1 genotypes associated with subclassifications of craniofacial asymmetry and severity of temporomandibular disorders.

INTRODUCTION: We investigated whether ACTN3, ENPP1, ESR1, PITX1, and PITX2 genes which contribute to sagittal and vertical malocclusions also contribute to facial asymmetries and temporomandibular disorders (TMD) before and after orthodontic and orthognathic surgery treatment. METHODS: One hundred seventy-four patients with a dentofacial deformity were diagnosed as symmetric or subdivided into 4 asymmetric groups according to posteroanterior cephalometric measurements. TMD examination diagnosis and jaw pain and function (JPF) questionnaires assessed the presence and severity of TMD. RESULTS: Fifty-two percent of the patients were symmetric, and 48% were asymmetric. The asymmetry classification demonstrated significant cephalometric differences between the symmetric and asymmetric groups, and across the 4 asymmetric subtypes: group 1, mandibular body asymmetry; group 2, ramus asymmetry; group 3, atypical asymmetry; and group 4, C-shaped asymmetry. ENPP1 SNP-rs6569759 was associated with group 1 (P = 0.004), and rs858339 was associated with group 3 (P = 0.002). ESR1 SNP-rs164321 was associated with group 4 (P = 0.019). These results were confirmed by principal component analysis that showed 3 principal components explaining almost 80% of the variations in the studied groups. Principal components 1 and 2 were associated with ESR1 SNP-rs3020318 (P <0.05). Diagnoses of disc displacement with reduction, masticatory muscle myalgia, and arthralgia were highly prevalent in the asymmetry groups, and all had strong statistical associations with ENPP1 rs858339. The average JPF scores for asymmetric subjects before surgery (JPF, 7) were significantly higher than for symmetric subjects (JPF, 2). Patients in group 3 had the highest preoperative JPF scores, and groups 2 and 3 were most likely to be cured of TMD 1 year after treatment. CONCLUSIONS: Posteroanterior cephalometrics can classify asymmetry into distinct groups and identify the probability of TMD and genotype associations. Orthodontic and orthognathic treatments of facial asymmetry are effective at eliminating TMD in most patients.

Nodal pathway genes are down-regulated in facial asymmetry.

PURPOSE: Facial asymmetry is a common comorbid condition in patients with jaw deformation malocclusion. Heritability of malocclusion is advancing rapidly, but very little is known regarding genetic contributions to asymmetry. This study identifies differences in expression of key asymmetry-producing genes that are down-regulated in patients with facial asymmetry. METHODS: Masseter muscle samples were collected during bilateral sagittal split osteotomy orthognathic surgery to correct skeletal-based malocclusion. Patients were classified as class II or III and open or deep bite malocclusion with or without facial asymmetry. Muscle samples were analyzed for gene expression differences on Affymetrix HT2.0 microarray global expression chips. RESULTS: Overall gene expression was different for asymmetric patients compared with other malocclusion classifications by principal component analysis (P < 0.05). We identified differences in the nodal signaling pathway, which promotes development of mesoderm and endoderm and left-right patterning during embryogenesis. Nodal and Lefty expression was 1.39- to 1.84-fold greater (P < 3.41 × 10), whereas integral membrane Nodal modulators Nomo1,2,3 were -5.63 to -5.81 (P < 3.05 × 10) less in asymmetry subjects. Fold differences among intracellular pathway members were negative in the range of -7.02 to -2.47 (P < 0.003). Finally Pitx2, an upstream effector of Nodal known to influence the size of type II skeletal muscle fibers was also significantly decreased in facial asymmetry (P < 0.05). CONCLUSIONS: When facial asymmetry is part of skeletal malocclusion, there are decreases in nodal signaling pathway genes in masseter muscle. This data suggest that the nodal signaling pathway is down-regulated to help promote development of asymmetry. Pitx2 expression differences also contributed to both skeletal and muscle development in this condition.

ACTN3 R577X genotypes associate with Class II and deepbite malocclusions.

INTRODUCTION: α-Actinins are myofibril anchor proteins that influence the contractile properties of skeletal muscles. ACTN2 is expressed in slow type I and fast type II fibers, whereas ACTN3 is expressed only in fast fibers. ACTN3 homozygosity for the 577X stop codon (ie, changing 577RR to 577XX, the R577X polymorphism) results in the absence of α-actinin-3 in about 18% of Europeans, diminishes fast contractile ability, enhances endurance performance, and reduces bone mass or bone mineral density. We have examined ACTN3 expression and genetic variation in the masseter muscle of orthognathic surgery patients to determine the genotype associations with malocclusion. METHODS: Clinical information, masseter muscle biopsies, and saliva samples were obtained from 60 subjects. Genotyping for ACTN3 single nucleotide polymorphisms, real-time polymerase chain reaction quantitation of muscle gene message, and muscle morphometric fiber type properties were compared to determine statistical differences between genotype and phenotype. RESULTS: Muscle mRNA expression level was significantly different for ACTN3 single nucleotide polymorphism genotypes (P <0.01). The frequency of ACTN3 genotypes was significantly different for the sagittal and vertical classifications of malocclusion, with the clearest association being elevated 577XX genotype in skeletal Class II malocclusion (P = 0.003). This genotype also resulted in significantly smaller diameters of fast type II fibers in masseter muscles (P = 0.002). CONCLUSION: ACTN3 577XX is overrepresented in subjects with skeletal Class II malocclusion, suggesting a biologic influence during bone growth. ACTN3 577XX is underrepresented in subjects with deepbite malocclusion, suggesting that muscle differences contribute to variations in vertical facial dimensions.

Epigenetic influence of KAT6B and HDAC4 in the development of skeletal malocclusion.

INTRODUCTION: Genetic influences on the development of malocclusion include heritable effects on both masticatory muscles and jaw skeletal morphology. Beyond genetic variations, however, the characteristics of muscle and bone are also influenced by epigenetic mechanisms that produce differences in gene expression. We studied 2 enzymes known to change gene expressions through histone modifications, chromatin-modifying histone acetyltransferase KAT6B and deacetylase HDAC4, to determine their associations with musculoskeletal variations in jaw deformation malocclusions. METHODS: Samples of masseter muscle were obtained from subjects undergoing orthognathic surgery from 6 malocclusion classes based on skeletal sagittal and vertical dysplasia. The muscles were characterized for fiber type properties by immunohistochemistry, and their total RNA was isolated for gene expression studies by microarray analysis and quantitative real-time polymerase chain reaction. RESULTS: Gene expressions for fast isoforms of myosins and contractile regulatory proteins and for KAT6B and HDAC4 were severalfold greater in masseter muscles from a patient with a deepbite compared with one with an open bite, and genes related to exercise and activity did not differ substantially. In the total population, expressions of HDAC4 (P = 0.03) and KAT6B (P = 0.004) were significantly greater in subjects with sagittal Class III than in Class II malocclusion, whereas HDAC4 tended to correlate negatively with slow myosin type I and positively with fast myosin gene, especially type IIX. CONCLUSIONS: These data support other published reports of epigenetic regulation in the determination of skeletal muscle fiber phenotypes and bone growth. Further investigations are needed to elucidate how this regulatory model might apply to musculoskeletal development and malocclusion.

A longitudinal assessment of sex differences in the growth of the mandibular retromolar space.

OBJECTIVE: To assess longitudinal variation in patterns of retromolar space growth, with regard to sex and cervical vertebrae maturation. DESIGN: We utilized serial lateral cephalograms from three craniofacial growth studies (Denver, Iowa, Oregon), measuring retromolar space and cervical vertebrae maturation in 99 subjects (56% male) from 8 to 18 years of age for each subject. Repeated measures ANOVA and a linear mixed effects model were used to assess retromolar space growth through time. RESULTS: Our analyses revealed an average increase in retromolar space of 8.73 mm from 8 to 18 years. While t-tests failed to find differences in retromolar space growth between males and females at the measured age points, repeated measures ANOVA and linear mixed effects models revealed modest differences in growth trends between sexes, with females having more growth earlier but a younger age of deceleration of growth (between 12 and 14 years of age). CONCLUSIONS: Our results confirm large increases in retromolar space through growth, reaching an average of 1.38 mm/year around puberty. Importantly, we add to the conversation regarding sex differences, showing differences in timing of growth. This highlights the importance of using longitudinal data and analytical approaches to address questions of this nature.

Condyle modeling stability, craniofacial asymmetry and ACTN3 genotypes: Contribution to TMD prevalence in a cohort of dentofacial deformities.

Craniofacial asymmetry, mandibular condylar modeling and temporomandibular joint disorders are common comorbidities of skeletally disproportionate malocclusions, but etiology of occurrence together is poorly understood. We compared asymmetry, condyle modeling stability and temporomandibular health in a cohort of 128 patients having orthodontics and orthognathic surgery to correct dentofacial deformity malocclusions. We also compared ACTN3 and ENPP1 genotypes for association to clinical conditions. Pre-surgical posterior-anterior cephalometric and panometric radiographic analyses; jaw pain and function questionnaire and clinical examination of TMD; and SNP-genotype analysis from saliva samples were compared to assess interrelationships. Almost half had asymmetries in need of surgical correction, which could be subdivided into four distinct morphological patterns. Asymmetric condyle modeling between sides was significantly greater in craniofacial asymmetry, but most commonly had an unanticipated pattern. Often, longer or larger condyles occurred on the shorter mandibular ramus side. Subjects with longer ramus but dimensionally smaller condyles were more likely to have self-reported TMD symptoms (p = 0.023) and significantly greater clinical diagnosis of TMD (p = 0 .000001), with masticatory myalgia most prominent. Genotyping found two significant genotype associations for ACTN3 rs1671064 (Q523R missense) p = 0.02; rs678397 (intronic SNP) p = 0.04 and one significant allele association rs1815739 (R577X nonsense) p = 0.00. Skeletal asymmetry, unusual condyle modeling and TMD are common and interrelated components of many dentofacial deformities. Imbalanced musculoskeletal functional adaptations and genetic or epigenetic influences contribute to the etiology, and require further investigation.

Quantification of myosin heavy chain RNA in human laryngeal muscles: differential expression in the vertical and horizontal posterior cricoarytenoid and thyroarytenoid.

BACKGROUND: Human laryngeal muscles are composed of fibers that express type I, IIA, and IIX myosin heavy chains (MyHC), but the presence and quantity of atypical myosins such as perinatal, extraocular, IIB, and alpha (cardiac) remain in question. These characteristics have been determined by biochemical or immunohistologic tissue sampling but with no complementary evidence of gene expression at the molecular level. The distribution of myosin, the main motor protein, in relation to structure-function relationships in this specialized muscle group will be important for understanding laryngeal function in both health and disease. OBJECTIVES: We determined the quantity of MyHC genes expressed in human posterior cricoarytenoid (PCA) and thyroarytenoid (TA) muscle using real-time quantitative reverse-transcriptase polymerase chain reaction in a large number of samples taken from laryngectomy subjects. The PCA muscle was divided into vertical (V) and horizontal (H) portions for analysis. RESULTS AND CONCLUSIONS: No extraocular or IIB myosin gene message is present in PCA or TA, but IIB is expressed in human extraocular muscle. Low but detectable amounts of perinatal and alpha gene message are present in both of the intrinsic laryngeal muscles. In H- and V-PCA, MyHC gene amounts were beta greater than IIA greater than IIX, but amounts of fast myosin RNA were greater in V-PCA. In TA, the order was beta greater than IIX greater than IIA. The profiles of RNA determined here indicate that, in humans, neither PCA nor TA intrinsic laryngeal muscles express unique very fast-contracting MyHCs but instead may rely on differential synthesis and use of beta, IIA, and IIX isoforms to perform their specialized contractile functions.

Condylar geometry variation is associated with ENPP1 variant in a population of patients with dento-facial deformities.

PURPOSE: Bone remodeling is essential in maintaining bone health. Considering that ENPP1 contributes to bone geometry and bone mineralization, the aim of our study was to analyze the association between single-nucleotide polymorphisms (SNPs) of ENPP1 and condylar remodeling. MATERIALS AND METHODS: A total of 156 patients undergoing orthodontic and maxillofacial surgery treatment for correction of malocclusion were included in this prospective study. Saliva samples from all subjects were used for DNA extraction and genotyping. Four ENPP1 SNPs were selected and tested to determine whether specific allelic variants are correlated with condylar remodeling. The criteria of condylar remodeling chosen were the ratio between each side of condylar height or surface differences on a dental panoramic of each patient. A diagnostic threshold was set at 15% difference between both sides. RESULTS: The ENPP1 SNP rs9373000 showed a statistically significant association with condylar height ratio >15% (p = 0.012). The GG genotype was found to be a protective factor against condylar height decrease (p = 0.003). CONCLUSION: This study identifies the genetic variant rs9373000 as a potentially causal variant for mandibular condyle geometry variation for patients presenting with dento-facial deformities.

Craniosacral therapy: the effects of cranial manipulation on intracranial pressure and cranial bone movement.

STUDY DESIGN: Quasi-experimental design. OBJECTIVES: To determine if physical manipulation of the cranial vault sutures will result in changes of the intracranial pressure (ICP) along with movement at the coronal suture. BACKGROUND: Craniosacral therapy is used to treat conditions ranging from headache pain to developmental disabilities. However, the biological premise for this technique has been theorized but not substantiated in the literature. METHODS: Thirteen adult New Zealand white rabbits (oryctolagus cuniculus) were anesthetized and microplates were attached on either side of the coronal suture. Epidural ICP measurements were made using a NeuroMonitor transducer. Distractive loads of 5, 10, 15, and 20 g (simulating a craniosacral frontal lift technique) were applied sequentially across the coronal suture. Baseline and distraction radiographs and ICP were obtained. One animal underwent additional distractive loads between 100 and 10,000 g. Plate separation was measured using a digital caliper from the radiographs. Two-way analysis of variance was used to assess significant differences in ICP and suture movement. RESULTS: No significant differences were noted between baseline and distraction suture separation (F = 0.045; P>.05) and between baseline and distraction ICP (F = 0.279; P>.05) at any load. In the single animal that underwent additional distractive forces, movement across the coronal suture was not seen until the 500-g force, which produced 0.30 mm of separation but no corresponding ICP changes. CONCLUSION: Low loads of force, similar to those used clinically when performing a craniosacral frontal lift technique, resulted in no significant changes in coronal suture movement or ICP in rabbits. These results suggest that a different biological basis for craniosacral therapy should be explored.

ENPP1 and ESR1 genotypes influence temporomandibular disorders development and surgical treatment response in dentofacial deformities.

UNLABELLED: Dentofacial deformities are dys-morpho-functional disorders involving the temporomandibular joints (TMJ). Many authors have reported a TMJ improvement in dysfunctional subjects with malocclusion after orthodontic or combined orthodontic and surgical treatment particularly for the relief of pain. In particular, few studies have highlighted the demographic and clinical predictors of response to surgical treatment. To date, no genetic factor has yet been identified as a predictor of response to surgical treatment. The aim of this cohort study is therefore to identify single-nucleotide polymorphisms associated with postoperative temporomandibular disorders (TMD) or with TMJ symptoms after orthognathic surgery. Here, we found the AA genotype of SNP rs1643821 (ESR1 gene) as a risk factor for dysfunctional worsening after orthognathic surgery. In addition, we have identified TT genotype of SNP rs858339 (ENPP1 gene) as a protective factor against TMD in a population of patients with dentofacial deformities. Conversely, the heterozygous genotype AT was identified as a risk factor of TMD with respect to the rest of our population. All these elements are particularly important to bring new screening strategies and tailor future treatment. PERSPECTIVE: This study allows us to identify sub-populations at high risk of developing postoperative temporomandibular disorders after orthognathic surgery procedures. Many other genes of interest could be potential factors influencing the dysfunctional response to orthognathic surgery, particularly genes of the Opera cohort.

Anatomy and fiber type composition of human interarytenoid muscle.

Intrinsic laryngeal muscle investigations, especially those of the interarytenoid (IA) muscle, have been primarily teleologically based. We determined IA muscle anatomy and histochemical and immunohistochemical classification of extrafusal and intrafusal (muscle spindle) fibers in 5 patients. Extrafusal fibers were oxidative type I and glycolytic types IIA and IIX. Intrafusal fibers of muscle spindles were identified by the presence of tonic and neonatal myosin. The results demonstrate that the IA muscle has a phenotype similar to that of limb skeletal muscle. Myosin coexpression, the absence of intrafusal fibers, and fiber type grouping were unusual features found previously in the thyroarytenoid and posterior cricoarytenoid muscles, but they were not present in the IA muscle. These findings lead to the conclusion that the IA muscle has functional significance beyond its assumed importance in maintaining vocal fold position during phonation. The presence of spindles demonstrates differences in motor control as compared to the thyroarytenoid and posterior cricoarytenoid muscles. Further, extrafusal fiber characteristics implicate IA muscle involvement in muscle tension dysphonia and adductor spasmodic dysphonia. Given the unique physiologic characteristics of the human IA muscle, further research into the role of the IA muscle in voice disorders is warranted.

Unloaded shortening velocity and myosin heavy chain variations in human laryngeal muscle fibers.

Myosin description in human laryngeal muscles is incomplete, but evidence suggests the presence of type I, IIA, IIX, and tonic myosin heavy chain (MHC) fibers. This study describes the unloaded shortening velocity (V0) of chemically skinned laryngeal muscle fibers measured by the slack test method in relation to MHC content. Skeletal fibers from human laryngeal and limb muscle biopsy specimens were obtained for determination of V0, and subsequently, glycerol-sodium dodecyl sulfate-polyacrylamide gel electrophoresis was used to determine the MHC isoform content. The fibers from human limb muscle had shortening speeds similar to those in previous reports on human skeletal fibers. Type I, IIA, and IIX fibers of laryngeal muscle had shortening speeds similar to those of fibers from limb muscle, but laryngeal fibers with heterogeneous MHC expression had a wide range of shortening speeds, some being nearly twice as fast as limb fibers. In addition, MHC isoform bands from human extraocular muscle comigrated with some bands from laryngeal muscle--a finding suggesting that extraocular myosin may also be expressed.

Muscle fiber type composition and effects of vocal fold immobilization on the two compartments of the human posterior cricoarytenoid: a case study of four patients.

The human posterior cricoarytenoid (PCA) muscle is divided into two compartments, the vertical and horizontal bellies, which contain differences in their myosin heavy chain (MyHC) composition. Using immunohistochemical techniques on whole PCA samples, this study provides a more thorough description of the fiber type composition of entire bellies of the PCA. Four patients provided complete PCA samples containing both compartments of their right and left sides; two with unilaterally immobilized vocal folds. The horizontal belly had 80% slow (type I) fibers and 20% fast (type II) fibers. The vertical belly contained equal amounts of slow and fast fibers (approximately 55%:45%); clearly distinguishing between two compartments. Atrophy of muscle fibers and fiber type grouping were also present in both normal and affected subjects; providing no clear confirmation of the clinical findings of vocal fold immobilization. Further study of the PCA muscle from patients with unilaterally immobilized vocal folds is needed.

Staining of human thyroarytenoid muscle with myosin antibodies reveals some unique extrafusal fibers, but no muscle spindles.

This study describes the myosin composition of extrafusal and intrafusal muscle fibers found in the human thyroarytenoid (TA) and sternohyoid (control) muscles. We sought to determine the presence of muscle spindles in the TA muscle, and to identify unusual extrafusal fiber types, using the commonly accepted approach of tissue staining with myosin isoform specific antibodies. Extrafusal fibers are organized into motor units, which subsequently produce muscle movement, whereas intrafusal fibers compose muscle spindles, the primary stretch receptor that provides afferent (feed back) information to the nervous system for regulation of motor unit length and tonicity. Immunohistochemical identification of muscle spindles was confirmed in sternohyoid, but not in TA samples; however, some extrafusal fibers contained tonic myosin. These results indicate that human TA muscle functions similar to some mammalian extraocular muscle, performing unloaded (non-weight bearing) contractions without afferent information from native muscle spindles.

Molecular motor MYO1C, acetyltransferase KAT6B and osteogenetic transcription factor RUNX2 expression in human masseter muscle contributes to development of malocclusion.

OBJECTIVE: Type I myosins are molecular motors necessary for glucose transport in the cytoplasm and initiation of transcription in the nucleus. Two of these, MYO1H and MYO1C, are paralogs which may be important in the development of malocclusion. The objective of this study was to investigate their gene expression in the masseter muscle of malocclusion subjects. Two functionally related proteins known to contribute to malocclusion were also investigated: KAT6B (a chromatin remodelling epigenetic enzyme which is activated by MYO1C) and RUNX2 (a transcription factor regulating osteogenesis which is activated by KAT6B). DESIGN: Masseter muscle samples and malocclusion classifications were obtained from orthognathic surgery subjects. Muscle was sectioned and immunostained to determine fibre type properties. RNA was isolated from the remaining sample to determine expression levels for the four genes by TaqMan(®) RT-PCR. Fibre type properties, gene expression quantities and malocclusion classification were compared. RESULTS: There were very significant associations (P<0.0000001) between MYO1C and KAT6B expressions. There were also significant associations (P<0.005) between RUNX2 expression and masseter muscle type II fibre properties. Very few significant associations were identified between MYO1C and masseter muscle fibre type properties. CONCLUSIONS: The relationship between MYO1C and KAT6B suggests that the two are interacting in chromatin remodelling for gene expression. This is the nuclear myosin1 (NM1) function of MYO1C. A surprising finding is the relationship between RUNX2 and type II masseter muscle fibres, since RUNX2 expression in mature muscle was previously unknown. Further investigations are necessary to elucidate the role of RUNX2 in adult masseter muscle.

In vivo oxygen consumption and hemoglobin levels in human thyroarytenoid muscle.

OBJECTIVES/HYPOTHESIS: Visible light spectroscopy (VLS) is the technology behind the Food and Drug Administration-approved TSTAT device that is used to monitor tissue oxygen (StO(2)) and relative total hemoglobin (rtHb) levels by measuring reflected visible light. The purpose of this novel, pilot study was to determine if VLS is a reliable and valid method of measuring StO(2) and rtHb levels in the human thyroarytenoid/lateral cricoarytenoid (TA-LCA) muscle complex, thus providing information about vocal fold muscle physiology. STUDY DESIGN: Pre-test/post-test with mulitple baselines and two conditions. METHODS: VLS measurements were taken at baseline, during exercise, and following recovery on six subjects using both noncontact channel-port endoscope (endo-probe) and laryngeal electromyography (LEMG) needle-guided techniques. RESULTS: The average baseline StO(2) was 69% (standard deviation [SD] = 3.6%) for the LEMG-guided probe and was 71.5% (SD = 2.8%) for the endo-probe. During phonation, the StO(2) for the LEMG-guided probe dropped to 59% (SD = 7%; P = .04). Mean rtHb measured by the LEMG probe rose from a baseline of 144 µM (SD = 165 µM) to 214 µM (SD = 166 µM, P = .34) during phonation and back to 149 µM (SD = 139 µM, P = .85) after recovery. Mean rtHb as measured using the endo-probe at baseline and after recovery was 104 µM (SD = 30 µM, P = .76). CONCLUSIONS: VLS can be used to measure changes in StO(2) and rtHb levels pre- and postexercise in the human TA-LCA muscle complex.