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Castel Guelfo di Bologna, Italy

Merlini L.,Laboratory of Musculoskeletal Cell Biology | Vagheggini A.,University of Blogna | Cocchi D.,University of Blogna
Frontiers in Aging Neuroscience | Year: 2014

Sarcopenia and muscular dystrophy (MD) are two conditions characterized by lower skeletal muscle quantity, lower muscle strength, and lower physical performance. Aging is associated with a peculiar alteration in body composition called "sarcopenic obesity" characterized by a decrease in lean body mass and increase in fat mass. To evaluate the presence of sarcopenia and obesity in a cohort of adult patients with MD, we have used the measurement techniques considered golden standard for sarcopenia that is for muscle mass dual-energy X-ray absorptiometry (DXA), for muscle strength hand-held dynamometry (HHD), and for physical performance gait speed. The study involved 14 adult patients with different types of MD. We were able to demonstrate that all patients were sarcopenic obese. We showed, in fact, that all were sarcopenic based on appendicular lean, fat and bone free, mass index (ALMI). In addition, all resulted obese according to the percentage of body fat determined by DXA in contrast to their body mass index ranging from underweight to obese. Skeletal muscle mass determined by DXA was markedly reduced in all patients and correlated with residual muscle strength determined by HHD, and physical performances determined by gait speed and respiratory function. Finally, we showed that ALMI was the best linear explicator of muscle strength and physical function. Altogether, our study suggests the relevance of a proper evaluation of body composition in MD and we propose to use, both in research and practice, the measurement techniques that has already been demonstrated effective in aging sarcopenia. © 2014 Merlini, Vagheggini and Cocchi.

Faenza I.,University of Bologna | Blalock W.,CNR Institute of Molecular Genetics | Bavelloni A.,Laboratory of Musculoskeletal Cell Biology | Schoser B.,Rizzoli Orthopaedic Institute | And 7 more authors.
FASEB Journal | Year: 2012

Phosphoinositide-phospholipase C β1 (PLCβ1) plays a crucial role in the initiation of the genetic program responsible for muscle differentiation. We previously demonstrated that nuclear PLCβ1 activates the cyclin D3 promoter during the differentiation of myoblasts to myotubes, indicating that PLCβ1 is essential for cyclin D3 promoter activation and gene transcription, through c-jun/AP1. Myotonic dystrophy (DM) is the most prevalent form of muscular dystrophy in adults. DM type 1 (DM1) and type 2 (DM2) are dominantly inherited multisystem disorders. DM1 is triggered by the pathological expansion of a (CTG)(n) triplet repeat in the gene coding for DMPK, the dystrophia myotonica-protein kinase, whereas a (CCTG)(n) tetranucleotide repeat expansion in the ZNF9 gene, encoding a CCHC-type zinc finger protein, causes DM2. We found that, unlike in normal myotubes, the level of expression of PLCβ1 in DM1 and DM2 cells was already elevated in proliferating cells. Treatment with insulin induced a dramatic decrease in the amount of PLCβ1. During differentiation, cyclin D3 and myogenin were elevated in normal myotubes, whereas differentiating DM1 and DM2 cells did not increase these proteins. Forced expression of PLCβ1 in DM1 and DM2 cells increased the expression of differentiation markers, myogenin and cyclin D3, and enhanced fusion of DM myoblasts. These results highlight again that PLCβ1 expression is a key player in myoblast differentiation, functioning as a positive regulator in the correction of delayed differentiation of skeletal muscle in DM human myoblasts. © FASEB.

Capanni C.,CNR Institute of Molecular Genetics | Squarzoni S.,CNR Institute of Molecular Genetics | Cenni V.,CNR Institute of Molecular Genetics | D'Apice M.R.,University of Rome Tor Vergata | And 7 more authors.
Cell Cycle | Year: 2012

Prelamin A processing impairment is a common feature of a restricted group of rare genetic alterations/disorders associated with a wide range of clinical phenotypes. Changes in histone posttranslational modifications, alterations in non-histone chromatin proteins and chromatin disorganization have been specifically linked to impairment of specific, distinct prelamin A processing steps, but the molecular mechanism involved in these processes is not yet understood . In this study, we show that the accumulation of wild-type prelamin A detected in restrictive dermopathy (RD), as well as the accumulation of mutated forms of prelamin A identified in familial partial lipodystrophy (FPLD) and mandibuloacral dysplasia (MADA), affect the nuclear localization of barrier-to-autointegration factor (BAF), a protein able to link lamin A precursor to chromatin remodeling functions. Our findings, in accordance with previously described results, support the hypothesis of a prelamin A involvement in BAF nuclear recruitment and suggest BAF-prelamin A complex as a protein platform usually activated in prelamin A-accumulating diseases. Finally, we demonstrate the involvement of the inner nuclear membrane protein emerin in the proper localization of BAF-prelamin A complex. © 2012 Landes Bioscience.

Sorato E.,University of Padua | Menazza S.,University of Padua | Zulian A.,University of Padua | Sabatelli P.,National Research Council Italy | And 8 more authors.
Free Radical Biology and Medicine | Year: 2014

Although mitochondrial dysfunction and oxidative stress have been proposed to play a crucial role in several types of muscular dystrophy (MD), whether a causal link between these two alterations exists remains an open question. We have documented that mitochondrial dysfunction through opening of the permeability transition pore plays a key role in myoblasts from patients as well as in mouse models of MD, and that oxidative stress caused by monoamine oxidases (MAO) is involved in myofiber damage. In the present study we have tested whether MAO-dependent oxidative stress is a causal determinant of mitochondrial dysfunction and apoptosis in myoblasts from patients affected by collagen VI myopathies. We find that upon incubation with hydrogen peroxide or the MAO substrate tyramine myoblasts from patients upregulate MAO-B expression and display a significant rise in reactive oxygen species (ROS) levels, with concomitant mitochondrial depolarization. MAO inhibition by pargyline significantly reduced both ROS accumulation and mitochondrial dysfunction, and normalized the increased incidence of apoptosis in myoblasts from patients. Thus, MAO-dependent oxidative stress is causally related to mitochondrial dysfunction and cell death in myoblasts from patients affected by collagen VI myopathies, and inhibition of MAO should be explored as a potential treatment for these diseases. © 2014 The Authors.

Di Martino A.,Biomedical University of Rome | Merlini L.,Laboratory of Musculoskeletal Cell Biology | Faldini C.,Istituto Ortopedico Rizzoli di Bologna
Expert Opinion on Therapeutic Targets | Year: 2013

Introduction: The cause of low back pain and the pathophysiology of lumbar pain and sciatica have recently been reconsidered basing on current knowledge on cellular and molecular mediators of inflammation. Several cytokines have been considered as potential therapeutic targets to contrast sciatica in patients with disc herniation, and supportive studies suggest a leading role of TNF-α in this contest: therefore, clinical trials have tested TNF-α inhibitors in the clinical setting of the patient with radicular pain secondary to an herniated disc. Areas covered: The current review deals with the autoimmune theory of disc herniation and its role in determining radiculopathy and neuropathic pain. It also reports the recent evidences that led to the introduction of anti-TNF-α drugs into the clinical setting as a biological therapy for radiculopathy and disc herniation. Expert opinion: Targeting the TNF-α pathway has demonstrated controversial effects in the tested study population and available results only report a short-term follow-up. More confirmatory studies in terms of long-term clinical results, complications, more effective route of administration and cost-effective analysis are required to establish the real role of this biological therapy in the treatment of patients with disc herniation and neuropathy. © 2013 Informa UK, Ltd.

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