Platelet-rich plasma (PRP) has received increasing interest in applied medicine, being widely used in clinical practice with the aim of stimulating tissue healing. Despite the reported clinical success, there is still a lack of knowledge when considering the biological mechanisms at the base of the activity of PRP during the process of muscle healing. The aim of the present study was to verify whether the local delivery of PRP modulates specific molecular events involved in the early stages of the muscle regeneration process. The right flexor sublimis muscle of anesthetized Wistar rats was mechanically injured and either treated with PRP or received no treatment. At day 2 and 5 after surgery, the animals were sacrificed and the muscle samples evaluated at molecular levels. PRP treatment increased significantly the mRNA level of the pro-inflammatory cytokines IL-1β, and TGF-β1. This phenomenon induced an increased expression at mRNA and/or protein levels of several myogenic regulatory factors such as MyoD1, Myf5 and Pax7, as well as the muscular isoform of insulin-like growth factor1 (IGF-1Eb). No effect was detected with respect to VEGF-A expression. In addition, PRP application modulated the expression of miR-133a together with its known target serum response factor (SRF); increased the phosphorylation of αB-cristallin, with a significant improvement in several apoptotic parameters (NF-κB-p65 and caspase 3), indexes of augmented cell survival. The results of the present study indicates that the effect of PRP in skeletal muscle injury repair is due both to the modulation of the molecular mediators of the inflammatory and myogenic pathways, and to the control of secondary pathways such as those regulated by myomiRNAs and heat shock proteins, which contribute to proper and effective tissue regeneration.

The multiple roles that have been associated with heat shock proteins (HSPs), inside and outside cells are remarkable. HSPs have been found to play a fundamental role in multiple stress conditions and to offer protection from subsequent insults. Exercise, because of the physiological stresses associated with it, is one of the main stimuli associated with a robust increase of different HSPs in several tissues. Given the combination of physiological stresses induced by exercise, and the ‘cross-talk’ that occurs between signaling pathways in different tissues, it is likely that exercise induces the HSP expression through a combination of ‘stressors’, among which reactive oxygen species (ROS) could play a major role. Indeed, although an imbalance between ROS production and antioxidant levels results in oxidative stress, causing damage to lipids, proteins, and nucleic acids with a possible activation of the programed cell death pathway, at moderate concentrations ROS play an important role as regulatory mediators in signaling processes. Many of the ROS-mediated responses actually protect the cells against oxidative stress and re-establish redox homeostasis. The aim of this review is to provide a critical update on the role of exercise-induced ROS in the modulation of the HSP's response, focusing on experimental results from animal and human studies where the link between redox homeostasis and HSPs’ expression in different tissues has been addressed.

DNA methylation is one of the most studied epigenetic mechanisms that play a pivotal role in regulating gene expression. The epigenetic component is strongly involved in aging-bone diseases, such as osteoporosis and osteoarthritis. Both are complex multi-factorial late-onset disorders that represent a globally widespread health problem, highlighting a crucial point of investigations in many scientific studies. In recent years, new findings on the role of DNA methylation in the pathogenesis of aging-bone diseases have emerged. The aim of this systematic review is to update knowledge in the field of DNA methylation associated with osteoporosis and osteoarthritis, focusing on the specific tissues involved in both pathological conditions.

Thioredoxin reductase 1 (TrxR1) is a selenocysteine-containing protein involved in cellular redox homeostasis which is downregulated in skeletal muscle differentiation. Here we show that TrxR1 decrease occurring during myogenesis is functionally involved in the coordination of this cellular process. Indeed, TrxR1 depletion reduces myoblasts growth by inducing an early myogenesis -related gene expression pattern which includes myogenin and Myf5 up-regulation and Cyclin D1 decrease. On the contrary, the overexpression of TrxR1 during differentiation delays myogenic process, by negatively affecting the expression of Myogenin and MyHC. Moreover, we found that miR-23a and miR-23b - whose expression was increased in the early stage of C2C12 differentiation - are involved in the regulation of TrxR1 expression through their direct binding to the 3′ UTR of TrxR1 mRNA. Interestingly, the forced inhibition of miR-23a and miR-23b during C2C12 differentiation partially rescues TrxR1 levels and delays the expression of myogenic markers, suggesting the involvement of miR-23 in myogenesis via TrxR1 repression. Taken together, our results depict for the first time a novel molecular axis, which functionally acts in skeletal muscle differentiation through the modulation of TrxR1 by miR-23.