Associations between ACTN3 and OPPERA pain-related genes in malocclusion

We have investigated an orthognathic surgery population to determine how variation in masticatory muscle gene expression and genotype plays a key role in development of both jaw-deformation malocclusion and temporomandibular joint disorders (TMD). A gene of particular interest is ACTN3 since the common R577X polymorphism results in α-actinin-3 protein loss, reduced myofiber Z-disc structural integrity in skeletal muscle and decreased osteoblast/osteoclast activity in bone formation. Secondly, since the prevalence of TMD in this population is quite high (30%) we sought to determine if genes related to pain processes─previously identified in the Orofacial Pain: Prospective Evaluation and Risk Assessment Study (OPPERA) were differentially expressed

Facial-muscle weakness, speech disorders and dysphagia are common in patients with classic infantile Pompe disease treated with enzyme therapy

Classic infantile Pompe disease is an inherited generalized glycogen storage disorder caused by deficiency of lysosomal acid α-glucosidase. If left untreated, patients die before one year of age. Although enzyme-replacement therapy (ERT) has significantly prolonged lifespan, it has also revealed new aspects of the disease. For up to 11 years, we investigated the frequency and consequences of facial-muscle weakness, speech disorders and dysphagia in long-term survivors. Sequential photographs were used to determine the timing and severity of facial-muscle weakness. Using standardized articulation tests and fibreoptic endoscopic evaluation of swallowing, we investigated speech and swallowing function in a subset of patients. This study included 11 patients with classic infantile Pompe disease. Median age at the start of ERT was 2.4 months (range 0.1-8.3 months), and median age at the end of the study was 4.3 years (range 7.7 months −12.2 years). All patients developed facial-muscle weakness before the age of 15 months. Speech was studied in four patients. Articulation was disordered, with hypernasal resonance and reduced speech intelligibility in all four. Swallowing function was studied in six patients, the most important findings being ineffective swallowing with residues of food (5/6), penetration or aspiration (3/6), and reduced pharyngeal and/or laryngeal sensibility (2/6). We conclude that facial-muscle weakness, speech disorders and dysphagia are common in long-term survivors receiving ERT for classic infantile Pompe disease. To improve speech and reduce the risk for aspiration, early treatment by a speech therapist and regular swallowing assessments are recommended

Clinical classification of cancer cachexia:phenotypic correlates in human skeletal muscle

Aim – To relate muscle phenotype to a range of current diagnostic criteria for cancer cachexia Methods – 41 patients with resectable upper gastrointestinal (GI) or pancreatic cancer underwent characterisation for cachexia based on weight-loss (WL) and / or low muscularity (LM). Four diagnostic criteria were used >5%WL, >10% WL, LM, and LM + >2%WL. Patients underwent biopsy of the rectus muscle. Analysis included immunohistochemistry for fibre size and type, protein and nucleic acid concentration, and Western blots for markers of autophagy, SMAD signalling, and inflammation. Results – Compared with non-cachectic cancer patients, if patients were classified by LM or LM + >2%WL, mean muscle fibre diameter was significantly reduced (p = 0.02 and p = 0.001) repectively. No difference in fibre diameter was observed if patients were classified with WL alone. Regardless of classification, there was no difference in fibre number or proportion of fibre type across all myosin heavy chain isoforms. Mean muscle protein content was reduced and the ratio of RNA/DNA decreased if patients were classified by either >5% WL or LM + >2%WL. Compared with non-cachectic patients, when patients were classified according to >5% WL, SMAD3 protein levels were increased (p=0.022) and with >10% WL, beclin (p = 0.05) and ATG5 (p = 0.01) protein levels were also increased. There were no differences in pNFkB or pSTAT3 levels across any of the groups. Conclusions – Whereas fibre type is not targeted selectively, muscle fibre size, biochemical composition and pathway phenotype can vary according to whether the criteria for cachexia include both a measure of low muscularity and weight loss

Specialized cranial muscles: how different are they from limb and abdominal muscles?

Mammalian skeletal muscle fibers can be classified into functional types by the heavy chain (MyHC) and light chain (MyLC) isoforms of myosin (the primary motor protein) that they contain. Most human skeletal muscle contains fiber types and myosin isoforms I, IIA and IIX. Some highly specialized muscle fibers in human extraocular and jaw-closing muscles express either novel myosins or unusual combinations of isoforms of unknown functional significance. Extrinsic laryngeal muscles may express the extraocular MyHC isoform for rapid contraction and a tonic MyHC isoform for slow tonic contractions. In jaw-closing muscles, fiber phenotypes and myosin expression have been characterized as highly unusual. The jaw-closing muscles of most carnivores and primates have tissue-specific expression of the type IIM or `type II masticatory' MyHC. Human jaw-closing muscles, however, do not contain IIM myosin. Rather, they express myosins typical of developing or cardiac muscle in addition to type I, IIA and IIX myosins, and many of their fibers are hybrids, expressing two or more isoforms. Fiber morphology is also unusual in that the type II fibers are mostly of smaller diameter than type I. By combining physiological and biochemical techniques it is possible to determine the maximum velocity of unloaded shortening (V(o)) of an individual skeletal muscle fiber and subsequently determine the type and amount of myosin isoform. When analyzed, some laryngeal fibers shorten at much faster rates than type II fibers from limb and abdominal muscle. Yet some type I fibers in masseter show an opposite trend towards speeds 10-fold slower than type I fibers of limb muscle. These unusual shortening velocities are most probably regulated by MyHC isoforms in laryngeal fibers and by MyLC isoforms in masseter. For the jaw-closing muscles, this finding represents the first case in human muscle of physiological regulation of kinetics by light chains. To gether, these results demonstrate that, compared to other skeletal muscles, cranial muscles have a wider repertoire of contractile protein expression and function. Molecular techniques for reverse transcription of mRNA and amplification by polymerase chain reaction have been applied to typing of single fibers isolated from limb muscles, successfully identifying pure type I, IIA and IIX and hybrid type I/IIA and IIA/IIX fibers. This demonstrates the potential for future studies of the regulation of gene expression in jaw-closing and laryngeal muscles, which have such a variety of complex fiber types fitting them for their roles in vivo

Masseter function and skeletal malocclusion

The aim of this work is to review the relationship between the function of the masseter muscle and the occurrence of malocclusions. An analysis was made of the masseter muscle samples from subjects who underwent mandibular osteotomies. The size and proportion of type-II fibers (fast) decreases as facial height increases. Patients with mandibular asymmetry have more type-II fibers on the side of their deviation. The insulin-like growth factor and myostatin are expressed differently depending on the sex and fiber diameter. These differences in the distribution of fiber types and gene expression of this growth factor may be involved in long-term postoperative stability and require additional investigations. Muscle strength and bone length are two genetically determined factors in facial growth. Myosin 1H (MYOH1) is associated with prognathia in Caucasians. As future objectives, we propose to characterize genetic variations using “Genome Wide Association Studies” data and their relationships with malocclusions

Fiber-type differences in masseter muscle associated with different facial morphologies

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 × 3 × 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