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1.
Oral Dis ; 29(1): 232-244, 2023 Jan.
Article in English | MEDLINE | ID: mdl-34773324

ABSTRACT

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.


Subject(s)
Bruxism , Humans , Bruxism/genetics , Actinin/genetics , Masseter Muscle , Self Report , Genotype
3.
Arch Oral Biol ; 143: 105547, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36162340

ABSTRACT

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.


Subject(s)
Mandible , Sex Characteristics , Adolescent , Cephalometry/methods , Child , Female , Humans , Male
4.
J Craniofac Surg ; 32(3): 1014-1021, 2021 May 01.
Article in English | MEDLINE | ID: mdl-32941210

ABSTRACT

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.


Subject(s)
Orthognathic Surgical Procedures , Osteogenesis, Distraction , Temporomandibular Joint Disorders , Adolescent , Adult , Aged , Child , Child, Preschool , Humans , Middle Aged , Retrospective Studies , Temporomandibular Joint , Young Adult
5.
PLoS One ; 15(7): e0236425, 2020.
Article in English | MEDLINE | ID: mdl-32726330

ABSTRACT

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.


Subject(s)
Actinin/genetics , Dentofacial Deformities/genetics , Genetic Predisposition to Disease , Phosphoric Diester Hydrolases/genetics , Pyrophosphatases/genetics , Temporomandibular Joint Disorders/genetics , Adult , Chin/diagnostic imaging , Dentofacial Deformities/diagnostic imaging , Dentofacial Deformities/pathology , Dentofacial Deformities/surgery , Face/diagnostic imaging , Female , Genetic Association Studies , Humans , Jaw/diagnostic imaging , Male , Malocclusion/diagnostic imaging , Malocclusion/genetics , Malocclusion/pathology , Malocclusion/surgery , Mandibular Condyle/diagnostic imaging , Mandibular Condyle/pathology , Mandibular Condyle/surgery , Models, Dental , Orthognathic Surgical Procedures , Polymorphism, Single Nucleotide/genetics , Temporomandibular Joint Disorders/diagnostic imaging , Temporomandibular Joint Disorders/pathology , Temporomandibular Joint Disorders/surgery
6.
J Oral Rehabil ; 46(4): 321-329, 2019 Apr.
Article in English | MEDLINE | ID: mdl-30472807

ABSTRACT

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.


Subject(s)
Bruxism/surgery , Malocclusion/surgery , Orthognathic Surgery , Postoperative Complications/physiopathology , Temporomandibular Joint Disorders/physiopathology , Adolescent , Adult , Aged , Bruxism/complications , Bruxism/epidemiology , Bruxism/physiopathology , Female , France/epidemiology , Habits , Humans , Male , Malocclusion/complications , Malocclusion/epidemiology , Malocclusion/physiopathology , Middle Aged , Postoperative Complications/epidemiology , Prospective Studies , Risk Factors , Temporomandibular Joint Disorders/epidemiology , Temporomandibular Joint Disorders/etiology , Young Adult
7.
Am J Orthod Dentofacial Orthop ; 152(5): 631-645, 2017 Nov.
Article in English | MEDLINE | ID: mdl-29103441

ABSTRACT

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.


Subject(s)
Dentofacial Deformities/classification , Dentofacial Deformities/genetics , Estrogen Receptor alpha/genetics , Facial Asymmetry/classification , Facial Asymmetry/genetics , Phosphoric Diester Hydrolases/genetics , Pyrophosphatases/genetics , Temporomandibular Joint Disorders/genetics , Adult , Dentofacial Deformities/complications , Dentofacial Deformities/surgery , Facial Asymmetry/complications , Facial Asymmetry/surgery , Female , Genotype , Humans , Male , Orthognathic Surgical Procedures , Postoperative Complications/etiology , Severity of Illness Index , Temporomandibular Joint Disorders/etiology
8.
J Craniomaxillofac Surg ; 45(6): 826-830, 2017 Jun.
Article in English | MEDLINE | ID: mdl-28381371

ABSTRACT

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.


Subject(s)
Anatomic Variation , Bone Remodeling/genetics , Mandibular Condyle/anatomy & histology , Maxillofacial Abnormalities/genetics , Phosphoric Diester Hydrolases/genetics , Polymorphism, Single Nucleotide , Pyrophosphatases/genetics , Adult , Alleles , Female , Genotype , Humans , Male , Prospective Studies
9.
J Craniomaxillofac Surg ; 44(9): 1226-37, 2016 Sep.
Article in English | MEDLINE | ID: mdl-27519661

ABSTRACT

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.


Subject(s)
Dentofacial Deformities/genetics , Dentofacial Deformities/surgery , Estrogen Receptor alpha/genetics , Phosphoric Diester Hydrolases/genetics , Pyrophosphatases/genetics , Temporomandibular Joint Disorders/genetics , Adult , Dentofacial Deformities/diagnostic imaging , Female , Genotype , Humans , Male , Orthognathic Surgical Procedures , Polymorphism, Single Nucleotide , Radiography, Panoramic , Risk Factors , Temporomandibular Joint Disorders/diagnostic imaging
10.
Am J Orthod Dentofacial Orthop ; 146(5): 603-11, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25439211

ABSTRACT

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.


Subject(s)
Actinin/genetics , Arginine/genetics , Malocclusion, Angle Class II/genetics , Overbite/genetics , Polymorphism, Genetic/genetics , Biopsy , Codon, Terminator/genetics , Cytosine , Exons/genetics , Female , Gene Frequency/genetics , Genetic Variation/genetics , Genotype , Humans , Introns/genetics , Male , Masseter Muscle/metabolism , Masseter Muscle/pathology , Muscle Fibers, Fast-Twitch/ultrastructure , Muscle Fibers, Skeletal/classification , Muscle Fibers, Skeletal/pathology , Phenotype , Polymorphism, Single Nucleotide/genetics , Real-Time Polymerase Chain Reaction/methods , Saliva/chemistry , Thymine , Young Adult
11.
J Craniofac Surg ; 25(6): e548-55, 2014 Nov.
Article in English | MEDLINE | ID: mdl-25364968

ABSTRACT

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.


Subject(s)
Down-Regulation/genetics , Facial Asymmetry/genetics , Nodal Protein/genetics , Signal Transduction/genetics , Adult , Facial Asymmetry/pathology , Female , Homeodomain Proteins/genetics , Humans , Intracellular Signaling Peptides and Proteins/genetics , Left-Right Determination Factors/genetics , Male , Malocclusion/genetics , Malocclusion/pathology , Masseter Muscle/metabolism , Masseter Muscle/pathology , Membrane Proteins/genetics , Transcription Factors/genetics , Homeobox Protein PITX2
12.
Arch Oral Biol ; 59(6): 601-7, 2014 Jun.
Article in English | MEDLINE | ID: mdl-24698832

ABSTRACT

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.


Subject(s)
Core Binding Factor Alpha 1 Subunit/genetics , Histone Acetyltransferases/genetics , Malocclusion/genetics , Masseter Muscle/metabolism , Myosin Type I/genetics , Female , Gene Expression , Humans , Male , Malocclusion/classification , Real-Time Polymerase Chain Reaction , Young Adult
13.
Am J Orthod Dentofacial Orthop ; 144(4): 568-76, 2013 Oct.
Article in English | MEDLINE | ID: mdl-24075665

ABSTRACT

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.


Subject(s)
Epigenomics , Histone Acetyltransferases/genetics , Histone Deacetylases/genetics , Masseter Muscle/drug effects , Open Bite/genetics , Overbite/genetics , Repressor Proteins/genetics , Female , Histone Acetyltransferases/pharmacology , Histone Deacetylases/pharmacology , Humans , Male , Malocclusion, Angle Class II/genetics , Malocclusion, Angle Class III/genetics , Myosins/genetics , Oligonucleotide Array Sequence Analysis , Repressor Proteins/pharmacology , Young Adult
14.
Laryngoscope ; 121(11): 2429-34, 2011 Nov.
Article in English | MEDLINE | ID: mdl-22020893

ABSTRACT

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.


Subject(s)
Hemoglobinometry , Laryngeal Muscles/physiology , Laryngoscopes , Light , Oxygen Consumption/physiology , Vocal Cords/physiology , Electromyography/instrumentation , Female , Humans , Phonation/physiology , Pilot Projects , Reference Values , Spectrum Analysis/instrumentation , Spectrum Analysis/methods , Voice Disorders/diagnosis , Voice Disorders/physiopathology
15.
Anat Rec (Hoboken) ; 294(7): 1170-7, 2011 Jul.
Article in English | MEDLINE | ID: mdl-21618442

ABSTRACT

It has been suggested recently that masticatory muscle size reduction in humans resulted in greater encephalization through decreased compressive forces on the cranial vault. Following this logic, if masticatory muscle size were increased, then a reduction in brain growth should also occur. This study was designed to test this hypothesis using a myostatin (GDF-8) knockout mouse model. Myostatin is a negative regulator of skeletal muscle growth, and individuals lacking this gene show significant hypermuscularity. Sixty-two [32 wild-type (WT) and 30 GDF-8 -/- knockout], 1, 28, 56, and 180-day-old CD-1 mice were used. Body and masseter muscle weights were collected following dissection and standardized lateral and dorsoventral cephalographs were obtained. Cephalometric landmarks were identified on the radiographs and cranial volume was calculated. Mean differences were assessed using a two-way ANOVA. KO mice had significantly greater body and masseter weights beginning at 28 days compared with WT controls. No significant differences in cranial volumes were noted between KO and WT. Muscle weight was not significantly correlated with cranial volume in 1, 28, or 180-day-old mice. Muscle weights exhibited a positive correlation with cranial volume at 56 days. Results demonstrate that masticatory hypermuscularity is not associated with reduced cranial volume. In contrast, there is abundant data demonstrating the opposite, brain growth determines cranial vault growth and masticatory apparatus only affects ectocranial morphology. The results presented here do not support the hypothesis that a reduction in masticatory musculature relaxed compressive forces on the cranial vault allowing for greater encephalization.


Subject(s)
Masseter Muscle/pathology , Masticatory Muscles/pathology , Myostatin/physiology , Skull/anatomy & histology , Animals , Male , Masseter Muscle/growth & development , Masticatory Muscles/growth & development , Mice , Mice, Knockout , Muscle Development , Skull/growth & development
16.
J Voice ; 25(4): 387-94, 2011 Jul.
Article in English | MEDLINE | ID: mdl-20685075

ABSTRACT

BACKGROUND: Mitochondrial alterations occur in skeletal muscle fibers throughout the normal aging process, resulting from increased accumulation of reactive oxide species (ROS). These result in respiratory chain abnormalities, which decrease the oxidative capacity of muscle fibers, leading to decreased contractile force, sarcopenia, or fiber necrosis. Intrinsic laryngeal muscles are a cranial muscle group that possesses some distinctive genotypic, phenotypic, and physiologic properties. Their susceptibility to mitochondrial alterations resulting from biological processes that increase levels of oxidative stress may be one of these distinctive characteristics. OBJECTIVES: The incidence of cytochrome c oxidase (COX) deficiency (COX(-)) was determined in human posterior cricoarytenoid (PCA) muscle when compared with the human thyrohyoid (TH) muscle, an extrinsic laryngeal muscle that served as "control" muscle. Ten PCA and 10 TH muscles were harvested postlaryngectomy from 10 subjects ranging in age from 55 to 86 years. Differences in COX(-) were compared within and between muscle types using tissue section staining and standard morphometric analysis. RESULTS AND CONCLUSIONS: COX(-) fibers were identified in both the PCA and TH muscles. The PCA muscle had 10 times as may affected fibers as the TH muscle, with significant differences in COX(-) found between muscle type and fiber type (P=0.003). Almost all of this effect was the result of elevated levels of COX(-) in type I fibers from the PCA muscle (P=0.002) that showed a strong positive correlation with increased age. These results suggest that increased mitochondrial alterations may occur in the PCA muscle during normal aging.


Subject(s)
Aging/metabolism , Electron Transport Complex IV/metabolism , Laryngeal Muscles/enzymology , Oxidative Stress , Aged , Aged, 80 and over , Humans , Male , Middle Aged , Muscle Fibers, Fast-Twitch/enzymology , Muscle Fibers, Slow-Twitch/enzymology
17.
Anat Rec (Hoboken) ; 293(1): 32-41, 2010 Jan.
Article in English | MEDLINE | ID: mdl-19899116

ABSTRACT

It is well recognized that masticatory muscle function helps determine morphology, although the extent of function on final form is still debated. GDF-8 (myostatin), a transcription factor is a negative regulator of skeletal muscle growth. A recent study has shown that mice homozygous for the myostatin mutation had increased muscle mass and craniofacial dysmorphology in adulthood. However, it is unclear whether such dysmorphology is present at birth. This study examines the onset and relationship between hypermuscularity and craniofacial morphology in neonatal and adult mice with GDF-8 deficiency. Fifteen (8 wild-type and 7 GDF-8 -/-), 1-day-old and 16 (9 wt and 7 GDF-8 -/-), 180-day-old male CD-1 mice were used. Standardized radiographs were taken of each head, scanned, traced, and cephalometric landmarks identified. Significant mean differences were assessed using a group x age, two-way ANOVA. Myostatin-deficient mice had significantly (P < 0.01) smaller body and masseter muscle weights and craniofacial skeletons at 1 day of age and significantly greater body and masseter muscle weights at 180 days of age compared to controls. Myostatin-deficient mice showed significantly (P < 0.001) longer and "rocker-shaped" mandibles and shorter and wider crania compared to controls at 180 days. Significant correlations were noted between masseter muscle weight and all cephalometric measurements in 180-day-old Myostatin-deficient mice. Results suggest that in this mouse model, there may be both early systemic skeletal growth deficiencies and later compensatory changes from hypermuscularity. These findings reiterate the role that masticatory muscle function plays on the ontogeny of the cranial vault, base, and most notably the mandible.


Subject(s)
Craniofacial Abnormalities/pathology , Masseter Muscle/pathology , Maxillofacial Development , Myostatin/physiology , Age Factors , Animals , Cephalometry , Craniofacial Abnormalities/etiology , Male , Masseter Muscle/growth & development , Mice , Mice, Knockout , Muscle Development , Organ Size
18.
Laryngoscope ; 118(3): 472-7, 2008 Mar.
Article in English | MEDLINE | ID: mdl-18091331

ABSTRACT

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.


Subject(s)
Laryngeal Muscles/metabolism , Myosin Heavy Chains/genetics , RNA/analysis , RNA/biosynthesis , Aged , Aged, 80 and over , Humans , Middle Aged
19.
J Orthop Sports Phys Ther ; 36(11): 845-53, 2006 Nov.
Article in English | MEDLINE | ID: mdl-17154138

ABSTRACT

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.


Subject(s)
Cranial Sutures , Intracranial Pressure , Musculoskeletal Manipulations , Animals , Complementary Therapies , Female , Male , Rabbits
20.
Am J Orthod Dentofacial Orthop ; 127(1): 37-46, 2005 Jan.
Article in English | MEDLINE | ID: mdl-15643413

ABSTRACT

BACKGROUND: The influence of muscle forces and associated physiologic behaviors on dental and skeletal development is well recognized but difficult to quantify because of the limited understanding of the interrelationships between physiologic and other mechanisms during growth. METHODS: The purpose of this study was to characterize fiber-type composition of masseter muscle in 44 subjects during surgical correction of malocclusion. Four fiber types were identified after immunostaining of biopsy sections with myosin heavy chain-specific antibodies, and the average fiber diameter and percentage of muscle occupancy of the fiber types were determined in each of 6 subject groups (Class II or Class III and open bite, normal bite, or deepbite). A 2 x 3 x 4 analysis of variance was used to determine significant differences between mean areas for fiber types, vertical relationships, and sagittal relationships. RESULTS: There were significant differences in percentage of occupancy of fiber types in masseter muscle in bite groups with different vertical dimensions. Type I fiber occupancy increased in open bites, and conversely, type II fiber occupancy increased in deepbites. The association between sagittal jaw relationships and mean fiber area was less strong, but, in the Class III group, the average fiber area was significantly different between the open bite, normal bite, and deepbite subjects. In the Class III subjects, type I and I/II hybrid fiber areas were greatly increased in subjects with deepbite. CONCLUSIONS: Given the variation between subjects in fiber areas and fiber numbers, larger subject populations will be needed to demonstrate more significant associations between sagittal relationships and muscle composition. However, the robust influence of jaw-closing muscles on vertical dimension allowed us to conclude that vertical bite characteristics vary according to the fiber type composition of masseter muscle.


Subject(s)
Face/anatomy & histology , Malocclusion/pathology , Masseter Muscle/cytology , Muscle Fibers, Skeletal/cytology , Adult , Analysis of Variance , Bite Force , Cephalometry , Humans , Malocclusion/physiopathology , Malocclusion/surgery , Masseter Muscle/physiology , Masseter Muscle/physiopathology , Muscle Fibers, Skeletal/classification , Vertical Dimension
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