Muscle-specific deletion of SLK/Stk2 enhances p38 activity and myogenesis in mdx mice.

Duchenne's muscular dystrophy (DMD) is a severe muscle wasting disorder characterized by the loss of dystrophin expression, muscle necrosis, inflammation and fibrosis. Ongoing muscle regeneration is impaired by persistent cytokine stress, further decreasing muscle function. Patients with DMD rarely survive beyond their early 20s, with cardiac and respiratory dysfunction being the primary cause of death.

Detection of S-100β Protein in Plasma and Urine After a Mild Traumatic Brain Injury.

This study assessed whether S-100β protein could be measured in urine when detectable in plasma after a mild traumatic brain injury (mTBI). Clinical data, plasma and urine samples were collected for the 46 adult patients prospectively enrolled in the emergency department (ED) of a Level 1 trauma center. S-100β protein concentrations were analysed using ELISA.

Targeting the Muscle-Bone Unit: Filling Two Needs with One Deed in the Treatment of Duchenne Muscular Dystrophy.

Purpose Of Review: In Duchenne muscular dystrophy (DMD), the progressive skeletal and cardiac muscle dysfunction and degeneration is accompanied by low bone mineral density and bone fragility. Glucocorticoids, which remain the standard of care for patients with DMD, increase the risk of developing osteoporosis. The scope of this review emphasizes the mutual cohesion and common signaling pathways between bone and skeletal muscle in DMD.

Utrophin haploinsufficiency does not worsen the functional performance, resistance to eccentric contractions and force production of dystrophic mice.

The lack of dystrophin in Duchenne muscular dystrophy (DMD) compromises the integrity and function of muscle fibers. Skeletal muscles, except the diaphragm, do not undergo progressive degeneration in adult mdx mice due to compensatory mechanisms, including structural protein upregulation. New mouse models, including utrophin haploinsufficient mdx (mdx/utrn+/-) mice, may better recapitulate DMD.

Genetic deletion of muscle RANK or selective inhibition of RANKL is not as effective as full-length OPG-fc in mitigating muscular dystrophy.

Although there is a strong association between osteoporosis and skeletal muscle atrophy/dysfunction, the functional relevance of a particular biological pathway that regulates synchronously bone and skeletal muscle physiopathology is still elusive. Receptor-activator of nuclear factor κB (RANK), its ligand RANKL and the soluble decoy receptor osteoprotegerin (OPG) are the key regulators of osteoclast differentiation and bone remodelling. We thus hypothesized that RANK/RANKL/OPG, which is a key pathway for bone regulation, is involved in Duchenne muscular dystrophy (DMD) physiopathology.

Osteoprotegerin and β-Agonists Mitigate Muscular Dystrophy in Slow- and Fast-Twitch Skeletal Muscles.

Our recent work showed that daily injections of osteoprotegerin (OPG)-immunoglobulin fragment complex (OPG-Fc) completely restore the function of fast-twitch extensor digitorum longus muscles in dystrophic mdx mice, a murine model of Duchenne muscular dystrophy. However, despite marked improvements, OPG-Fc was not as effective in preventing the loss of function of slow-twitch soleus and diaphragm muscles. Because β-agonists enhance the function of slow- and fast-twitch dystrophic muscles and because their use is limited by their adverse effects on bone and cardiac tissues, we hypothesized that OPG-Fc, a bone and skeletal muscle protector, acts synergistically with β-agonists and potentiates their positive effects on skeletal muscles.

A short-term statin treatment changes the contractile properties of fast-twitch skeletal muscles.

Background: Cumulative evidence indicates that statins induce myotoxicity. However, the lack of understanding of how statins affect skeletal muscles at the structural, functional, and physiological levels hampers proper healthcare management. The purpose of the present study was to investigate the early after-effects of lovastatin on the slow-twitch soleus (Sol) and fast-twitch extensor digitorum longus (EDL) muscles.

Physiological role of receptor activator nuclear factor-kB (RANK) in denervation-induced muscle atrophy and dysfunction.

The bone remodeling and homeostasis are mainly controlled by the receptor-activator of nuclear factor kB (RANK), its ligand RANKL, and the soluble decoy receptor osteoprotegerin (OPG) pathway. While there is a strong association between osteoporosis and skeletal muscle dysfunction, the functional relevance of a particular biological pathway that synchronously regulates bone and skeletal muscle physiopathology remains elusive. Our recent article published in the American Journal of Physiology (Cell Physiology) showed that RANK is also expressed in fully differentiated C2C12 myotubes and skeletal muscles.

Muscle RANK is a key regulator of Ca2+ storage, SERCA activity, and function of fast-twitch skeletal muscles.

Receptor-activator of nuclear factor-κB (RANK), its ligand RANKL, and the soluble decoy receptor osteoprotegerin are the key regulators of osteoclast differentiation and bone remodeling. Here we show that RANK is also expressed in fully differentiated myotubes and skeletal muscle. Muscle RANK deletion has inotropic effects in denervated, but not in sham, extensor digitorum longus (EDL) muscles preventing the loss of maximum specific force while promoting muscle atrophy, fatigability, and increased proportion of fast-twitch fibers.

Motor hypertonia and lack of locomotor coordination in mutant mice lacking DSCAM.

Down syndrome cell adherence molecule (DSCAM) contributes to the normal establishment and maintenance of neural circuits. Whereas there is abundant literature regarding the role of DSCAM in the neural patterning of the mammalian retina, less is known about motor circuits. Recently, DSCAM mutation has been shown to impair bilateral motor coordination during respiration, thus causing death at birth.

[Statin intolerance and associated muscular dysfunctions].

Hypercholesterolemia is a major risk factor for cardiovascular diseases. The 2012-2013 survey of Canada's public health measures revealed that dyslipidemia was present in 38% of the respondents aged between 18 and 79 years. According to the American College of Cardiology, the American Heart Association, the Canadian Cardiovascular Society and the Canadian Working Group Consensus, statins remain the treatment of choice for dyslipidemia and the reduction of cardiovascular risk.

Macrophage depletion reduces cell proliferation and extracellular matrix accumulation but increases the ultimate tensile strength of injured Achilles tendons.

Macrophages are present in large numbers and display specific and distinct phenotypes during the various phases of tissue repair. However, their role following tendon injury and during repair has never been investigated. We injected C57BL/6 mice daily for 4 days with liposome-encapsulated clodronate to deplete circulating monocytes/macrophages.