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Several chronic conditions leading to skeletal muscle dysfunction are known to be associated with changes in the expression of myosin heavy chain (MHC) isoforms at both the mRNA and protein level. Many of these conditions are modelled, pre-clinically, in the guinea pig due to similar disease onset and progression to the human condition, and their g...
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... all other species described, the myosin heavy chain family of genes is located on a single chromosome and arranged in a head to tail fashion in the order MyH3/ MyH2, MyH1/MyH 4 and MyH8/MyH13 with the excep- tion of the cardiac (MyH7α) and slow skeletal muscle iso- forms (MyH7β) which are located on a distant chromosome [2]. Using this knowledge, and the previ- ously determined location of the MyH2 gene as a starting point, we were able to advance along the genomic sequence data (Ensemble release 56), aligning individual exons from both Rattus norvegicus and Mus musculus MyH1, MyH2, MyH3, MyH4, MyH8 and MyH13 cDNAs (Table 2) to the guinea pig gDNA database, thus spatially mapping out the arrangement of genes in the guinea pig (Figure 1). During the course of this study, a full length cDNA pertaining to Cavia porcellus MyH7 was anno- tated in Ensemble release 56. ...
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Citations
... The ligament was then transected again at the femoral end to remove the portion overlying the meniscus. The meniscus was freed from the fine connective tissue, allowing a full thickness, medial meniscal transection (25). ...
... Both overproduction of IL-6 and decreased CS activity are associated with lower muscle strength and muscle weakness in various animal disease models (29,30). MHC typing change is one of the major causes of muscle weakness in various pathogenic situations (25,31). Decreased MHC IIa fiber is associated with lower muscle strength/muscle weakness in the quadriceps in patients with OA (32). ...
Background:
Osteoarthritis (OA) is the most common cause of joint pain, affecting approximately 15% of the population. Recent studies indicate that quadriceps muscle weakness is directly involved in the pathogenesis of OA-associated joint pain. Oxidative stress plays an important role in skeletal muscle dysfunction. Sesame oil is a natural product with excellent antioxidative property. However, whether sesame oil can decrease OA-induced joint pain has never been investigated.
Objective:
The aim of the present study was to examine the effect of sesame oil on OA-induced joint pain in rats.
Design:
OA-associated joint pain in rats was induced by medial meniscal transection in rats. Sesame oil (0, 1, 2, or 4 ml/kg/day, orally) was given to rats 7 days after OA induction, while the parameters were determined 7 days after sesame oil administration.
Results:
Daily sesame oil treatment for 7 days significantly decreased OA-associated joint pain. Sesame oil decreased muscular interleukin-6 and increased citrate synthase activity and myosin heavy chain IIa mRNA expression. Furthermore, sesame oil decreased muscular lipid peroxidation, nuclear Nrf2 protein expression, and reactive oxygen species generations as well as increased glutathione production and glutathione peroxidase activity in OA rats.
Conclusions:
Sesame oil may relieve OA-associated joint pain by inhibiting quadriceps muscular oxidative stress, at least partially, in rats.
... Myosin ATPase is localized to the globular head of the myosin heavy chain (MHC) [10]. MHC alteration plays a dominant role in muscle strength [11][12][13][14][15]. For example, decreased muscular MHC IIa mRNA and protein expressions are associated with muscle weakness in OA patients [16]. ...
... Muscle dysfunction can be detected in the early stage of MNX-induced OA. Previous stud-ies suggest that muscle weakness may be a result of disuse after MNX [14]; however, recent evidences show that muscle weakness may participate in the pathogenesis and development of OA [8]. In the present study, increased IL-6 and as well as decreased CS activity and MHC IIa mRNA expression were found from 7 days after MNX, which indicated that muscle weakness could be found in the early stage of MNX-induced OA. ...
... Inhibiting MHC IIa gene expression may be associated with muscular weakness after MNX. MHC typing changes have been suggested as one of the major causes of muscle weakness after MNX [14]. Decreased MHC IIa fiber is associated with lower muscle strength/muscle weakness in the quadriceps in patients with OA [42]. ...
Osteoarthritis is the most common form of arthritis, affecting approximately 15% of the population. Quadriceps muscle weakness is one of the risk factors of osteoarthritis development. Oxidative stress has been reported to play an important role in the pathogenesis of various muscle dysfunction; however, whether it is involved in osteoarthritis-associated quadriceps muscle weakness has never been investigated. The aim of the present study is to examine the involvement of oxidative stress in quadriceps muscle dysfunction in the initiation of osteoarthritis in rats. Rat osteoarthritis was initiated by conducting meniscectomy (MNX). Quadriceps muscle dysfunction was evaluated by assessing muscular interleukin-6, citrate synthase activity, and myosin heavy chain IIa mRNA expression levels. Muscular oxidative stress was assessed by determining lipid peroxidation, Nrf2 expression, reactive oxygen species, and circulating antioxidants. Increased muscular interleukin-6 production as well as decreased citrate synthase activity and myosin heavy chain IIa mRNA expression were observed at 7 and 14 days after MNX. Biomarkers of oxidative stress were significantly increased after MNX. Muscular free radical counts were increased while glutathione and glutathione peroxidase expression were decreased in MNX-treated rats. We conclude that oxidative stress may be involved in the pathogenesis of muscle dysfunction in MNX-induced osteoarthritis.
... Despite all mammals carrying the gene (MYH4) encoding MyHC IIB, extensive characterization has revealed a striking divide between large and small mammals with regard to MYH4 expression. Most small mammals such as mice [2], rats [2], rabbits [2,11], and guinea pigs [12,13] express MYH4 but most larger mammals such as cows [14], sheep [15] horses [16], goats [17], cats [18,19], dogs [20], baboons [19] and humans [2,21] do not express. Interestingly, domesticated pigs remain an anomaly amongst the large mammals as they express high levels of MYH4 [22,23], a phenotype likely exacerbated by the intensive selection pressure for enhanced muscle growth in these animals [24,25]. ...
Due to its similarity to humans, the pig is increasingly being considered as a good animal model for studying a range of human diseases. Despite their physiological similarities, differential expression of the myosin heavy chain (MyHC) IIB gene (MYH4) exists in the skeletal muscles of these species, which is associated with a
different muscle phenotype. The expression of different MyHC isoforms is a critical determinant of the contractile and metabolic characteristics of the muscle fibre. We aimed to elucidate whether a genomic mechanism was responsible for the drastically different expression of MYH4 between pigs and humans, thus improving our understanding of the pig as a model for human skeletal muscle research. We utilized approximately 1 kb of the MYH4 promoter from a domestic pig and a human (which do and do not express MYH4, respectively) to elucidate the role of the promoter sequence in regulating the high expression of MYH4 in porcine skeletal muscle. We identified a 3 bp genomic difference within the proximal CArG and Ebox
region of the MYH4 promoter of pigs and humans that dictates the differential activity of these promoters during myogenesis. Subtle species-specific genomic differences within the CArG-box region caused differential protein-DNA interactions at this site and is likely accountable for the differential MYH4 promoter activity
between pigs and humans. We propose that the genomic differences identified herein explain the differential activity of the MYH4 promoter of pigs and humans, which may contribute to the differential expression patterns displayed in these otherwise physiologically similar mammals. Further, we report that both the pig and
human MYH4 promoters can be induced by MyoD over-expression, but the capacity to activate the MYH4 promoter is largely influenced by the 3 bp difference located within the CArG-box region of the proximal MYH4 promoter.
... At all ages, we characterised contractile and metabolicassociated factors in the quadriceps muscle and determined OA severity through histopathological staining of knee joint sections. Subtle changes in factors associated with muscle contractility were determined using a set of oligonucleotide primers developed and qualified specifically for this purpose [36] (Table 1). ...
... The characteristics of skeletal muscles are a function of the contractile and metabolic properties of the muscle fibres from which they are composed. Contractile properties of the quadriceps skeletal muscle were assessed by the expression of myosin heavy chain (MHC) isoform mRNAs at each study time point as previously described [36,38]. Although many isoforms of MHC have been described, four are associated with adult skeletal muscle. ...
... MHC IIX mRNA was elevated at 3 months of age (approximately 3.5-fold), coincident with the first histopathological sign of OA (P ≤0.05); furthermore, it was positively correlated with total pathology grade at this time. MHC IIX mRNA is associated with the expression of fasttwitch glycolytic muscle fibres and is the second fastest MHC isoform in many laboratory species including the mouse, rat [51] and guinea pig [36]. Conversely, MHC IIX is the fastest MHC isoform in the human [52], which generally lacks MHC IIB expressing muscle fibres. ...
Osteoarthritis (OA) is the most common joint disorder in the world and represents the leading cause of pain and disability in the elderly population. Advancing age remains the single greatest risk factor for OA. Several studies have characterised disease development in the guinea pig ageing model of OA in terms of its joint histopathology and inflammatory cytokine profile. However, the quadriceps muscle has yet to be studied in relation to age-related disease onset or early disease progression. Therefore, we examined whether the initiation of OA in the Dunkin Hartley guinea pig is associated with changes in the quadriceps skeletal muscle. Male Dunkin Hartley guinea pigs (N = 24) were group housed with free access to standard guinea pig chow and water. At 2, 3, 5 and 7 months of age, six animals were selected based on their proximity to the median weight of the cohort. OA severity was graded at each time point by the assessment of toluidine blue stained step coronal sections of the total knee joint. Serum CTX II was measured as a potential biomarker of OA severity. Myosin Heavy Chain (MHC) isoforms were determined by a validated real-time PCR assay. Oxidative and glycolytic potential was determined in quadriceps homogenates via the measurement of ICDH and LDH activity.
Initiation of OA in the DH strain guinea pig occurred between 2 and 3 months of age and progressed until 7 months when the final analyses were conducted. Serum CTX II significantly decreased during this early period of OA initiation and levels were unrelated to the histopathological severity of knee OA at any of the time points assessed. MHC mRNA measurements revealed a significant elevation in MHC IIX mRNA (associated with fast-twitch skeletal muscle fibres) coincident with the initiation of OA at 3 months of age, with preliminary findings suggestive of a positive correlation to OA severity at this time point.
These preliminary findings suggest that disease initiation in the ageing guinea pig model of OA is not associated with overt quadriceps muscle atrophy but instead is coincident with altered expression of mRNAs associated with quadriceps skeletal muscle contractile properties (specifically fast-twitch MHC IIX).
... Pathway analysis clustered genes encoding myofibrillar proteins within the calcium signaling pathway. Expression of MYH4 encoding myosin heavy chain (MHC) isoform IIb (Tonge et al., 2010) dramatically decreased in PSE samples (FC = −26.1). In contrast, α actin (ACTA1) was upregulated (FC = 3.7). ...
... Interestingly, whereas MYH4 (which encodes fast-twitch glycolytic MHCIIb) was downregulated, MYH2 (which encodes fast-twitch oxidative glycolytic MHCIIa) and MYH1 (intermediate between type IIa and IIb MHCIIx) showed upregulation. Because turkey breast muscle mainly consists of fast-twitch glycolytic muscle fibers (Rosser et al., 1996), we hypothesized that the change in transcript abundance of MYH gene family members in the PSE turkey may cause fast-to-slow muscle transformation that is associated with various functional changes at the muscle cell level as well as cytosol-regulating Ca 2+ dynamics (Kaprielian et al., 1991;Jakubiec-Puka et al., 1999;Pette and Vrbová, 1999;Pette and Staron, 2001;Tonge et al., 2010). However, previous reports on the relative proportion of myosin heavy-chain isoforms in PSE meat have not been consistent (Ryu and Kim, 2006;Franck et al., 2007;Golding-Myers et al., 2010). ...
In response to high consumer demand, turkeys have been intensively selected for rapid growth rate and breast muscle mass and conformation. The success in breeding selection has coincided with an increasing incidence of pale, soft, and exudative (PSE) meat defect, especially in response to heat stress. We hypothesized that the underlying mechanism responsible for the development of PSE meat arises from differences in expression of several critical genes. The objective of this study was to determine differential gene expression between normal and PSE turkey meat using a 6K turkey skeletal muscle long oligonucleotide microarray. Breast meat samples were collected from Randombred Control Line 2 turkeys at 22 wk of age, and classified as normal or PSE primarily based on marinade uptake (high = normal, low = PSE). Total RNA was isolated from meat samples with the highest (normal, n = 6) and the lowest (PSE, n = 6) marinade uptake. Microarray data confirmation was conducted using quantitative real-time PCR. Selection of differentially expressed genes for pathway analysis was performed using a combination of fold change (FC) ranking (FC < -1.66, FC >1.66) and false discovery rate (<0.35) as criteria. The calcium signaling pathway was highlighted as the top canonical pathway associated with differential gene expression between normal and PSE turkey. Dramatic downregulation of fast-twitch myosin heavy chain coupled with upregulation of slow-twitch myosin and troponin C suggested a switch of skeletal muscle isoforms, which may alter muscle fiber arrangement and formation of actin-myosin complexes. Changes in expression of genes in the actin cytoskeleton signaling pathway also suggest altered structures of actin filaments that may affect cell motility as well as strength and flexibility of muscle cells. Substantial downregulation of pyruvate dehydrogenase kinase, isozyme 4 was observed in PSE samples, suggesting altered regulation of the aerobic metabolic pathway in the birds that developed PSE meat defect.
... One isoform is expressed in slow muscles (type I) and three isoforms are expressed in fast muscles (type II: IIA, IIX, and IIB). The exceptionally fast type IIB myosin is expressed in rabbit m. longissimus dorsi but does not occur in humans [22]. The expression of skeletal myosin isoforms varies during ontogenesis and in the postnatal period depending on the motor activity of some or other groups of muscles [19], as well as in case of myopathy and muscle fiber damage [23]. ...
The interaction between myosin and actin in striated muscle tissue is regulated by Ca2+ via thin filament regulatory proteins. Skeletal muscle possesses a whole pattern of myosin and tropomyosin isoforms. The regulatory effect of tropomyosin on actin-myosin interaction was investigated by measuring the sliding velocity of both actin and actin-tropomyosin filaments over fast and slow skeletal myosins using the in vitro motility assay. The actin-tropomyosin filaments were reconstructed with tropomyosin isoforms from striated muscle tissue. It was found that tropomyosins with different content of α-, β-, and γ-chains added to actin filaments affect the sliding velocity of filaments in different ways. On the other hand, the sliding velocity of filaments with the same content of α-, β-, and γ-chains depends on myosin isoforms of striated muscle. The reciprocal effects of myosin and tropomyosin on actin-myosin interaction in striated muscle may play a significant role in maintenance of effective work of striated muscle both during ontogenesis and under pathological conditions.
... Samples were then stored frozen (K80 8C) before first-strand cDNA synthesis using random hexamer primers, as described previously (Hemmings et al. 2009). Quantitative PCR was performed in duplicate using SYBR1 Master mix (Roche), 384-well microplates and the LightCycler LC480 (Roche) configured for SYBR green detection, again as described previously (Tonge et al. 2010). The primers for each transcript were designed using Primer Express (Applied Biosystems) and are shown inTable 1. ...
Fat infiltration within muscle is one of a number of features of vitamin D deficiency which leads to a decline in muscle functionality. The origin of this fat is unclear but one possibility is that it forms from myogenic precursor cells present in the muscle, which transdifferentiate into mature adipocytes. The current study examined the effect of the active form of vitamin D3, 1,25 dihydroxyvitamin D3 (1,25(OH)2D3), on the capacity of the C2C12 muscle cell line to differentiate towards the myogenic and adipogenic lineages. Cells were cultured in myogenic or adipogenic differentiation media containing increasing concentrations (0, 10-13, 10-11, 10-9, 10-7 or 10-5M) of 1,25(OH)2D3 for up to 6 days and markers of muscle and fat development measured.Mature myofibres were formed in both adipogenic and myogenic media, but fat droplets were only observed in adipogenic media. Relative to controls, low physiological concentrations (10-13 and 10-11M) of 1,25(OH)2D3 increased fat droplet accumulation, whereas high physiological (10-9M) and supraphysiological concentrations (≥10-7M) inhibited fat accumulation. This increased accumulation of fat with low physiological concentrations (10-13 and 10-11M) was associated with a sequential up-regulation of PPARγ2 and FABP4 mRNA, indicating formation of adipocytes, whereas higher concentrations (≥10-9M) reduced all these effects, and the highest concentration (10-5M) appeared to have toxic effects.This is the first study to demonstrate dose-dependent effects of 1,25(OH)2D3 on the transdifferentiation of muscle cells into adipose cells. Low physiological concentrations (possibly mimicking a deficient state) induced adipogenesis, whereas higher (physiological and supraphysiological) concentrations attenuated this effect.
... Bands 1 and 2 and 3–5 were cut separately for protein identification using mass spectrometry.Table 2 shows various MHC isoforms detected from these five bands in the UniprotKB protein database. The literature commonly terms myosin-1, -2, -4, and ‐7 as MHC IIX, IIA, IIB, and I (Richmond et al., 2001; Tonge et al., 2010; Weiss and Leinwand, 1996).Fig. 3 shows examples of MS/MS spectra for unique peptides identified in each of these proteins. ...
We studied the modulating role of cardiac myosin-binding protein C (cMyBP-C) in tropomyosin regulation of the actin-myosin interaction. The effect of cMyBP-C on the velocity of actin-tropomyosin filament sliding over cardiac and slow skeletal myosins was evaluated using in vitro motility assay. The effect of cMyBP-C on the actin-tropomyosin filaments sliding depended on the type of myosin. The regulatory effect of cMyBP-C differs for cardiac and slow skeletal myosin because of the presence of specific essential light chain (LC1sa) in slow skeletal myosin isoform.
Osteoarthritis (OA) is the most common form of arthritis, affecting approximately 15% of the population. The aim of this study was to evaluate the efficacy of sesame oil in controlling OA pain in rats. Rat joint pain was induced by medial meniscal transection in Sprague–Dawley rats and assessed by using hindlimb weight distribution method. Muscular oxidative stress was assessed by determining lipid peroxidation, reactive oxygen species and circulating antioxidants. Sesame oil significantly decreased joint pain compared with positive control group in a dose-dependent manner. Sesame oil decreased lipid peroxidation in muscle but not in serum. Further, sesame oil significantly decreased muscular superoxide anion and peroxynitrite generations but increased muscular glutathione and glutathione peroxidase levels. Further, sesame oil significantly increased nuclear factor erythroid-2-related factor (Nrf2) expression compared with positive control group. We concluded that daily sesame oil supplement may attenuate early joint pain by inhibiting Nrf2-associated muscular oxidative stress in OA rat model.
