Abstract
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.
Highlights
Musculoskeletal injures are the most common cause of severe long-term pain and physical disability, affecting hundreds of millions of people around the world and accounting for the majority of all sport-related injured [1]
Real time PCR analysis revealed that mRNA transcripts for cytokines, myogenic response factors (MRFs) and growth factors (GFs) were differently modulated from the presence of platelet-rich plasma (PRP) (Figure 1)
At both experimental post-injury points there was an increase in the transcriptional levels of TNFa, IL-6 and IL-10 mRNA in the injured muscles when compared with control (p, 0.05), without differences between groups treated or not with PRP (p.0.05) (Figure 1A)
Summary
Musculoskeletal injures are the most common cause of severe long-term pain and physical disability, affecting hundreds of millions of people around the world and accounting for the majority of all sport-related injured [1]. In addition to health care expenditures, the social cost of these injuries includes lost job wages and production. The rapidly increasing understanding of the contribution of growth factors (GFs) in the healing of injured tissue has given rise to a great interest in the use of autologous platelet-rich plasma (PRP) as a new therapeutic tool in the field of dentistry, dermatology, plastic and maxillofacial surgery, acute trauma, chronic tendinopathies, cosmetic surgery, veterinary medicine, and in muscle strain injuries [2,3,4,5,6,7,8]. Autologous PRP is obtained from the separation of whole blood into plasma and red cell constituents, with the subsequent concentration of platelets into a small volume of plasma. PRP is an example of autologous biomaterial product applied and studied since the 1980s [10,11,12]
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