scholarly journals Treatment of Skeletal Muscle Injury: A Review

2012 ◽  
Vol 2012 ◽  
pp. 1-7 ◽  
Author(s):  
L. Baoge ◽  
E. Van Den Steen ◽  
S. Rimbaut ◽  
N. Philips ◽  
E. Witvrouw ◽  
...  

Skeletal muscle injuries are the most common sports-related injuries and present a challenge in primary care and sports medicine. Most types of muscle injuries would follow three stages: the acute inflammatory and degenerative phase, the repair phase and the remodeling phase. Present conservative treatment includes RICE (rest, ice, compression, elevation), nonsteroidal anti-inflammatory drugs (NSAIDs) and physical therapy. However, if use improper, NSAIDs may suppress an essential inflammatory phase in the healing of injured skeletal muscle. Furthermore, it remains controversial whether or not they have adverse effects on the healing process or on the tensile strength. However, several growth factors might promote the regeneration of injured skeletal muscle, many novel treatments have involved on enhancing complete functional recovery. Exogenous growth factors have been shown to regulate satellite cell proliferation, differentiation and fusion in myotubes in vivo and in vitro, TGF-β1 antagonists behave as inhibitors of TGF-β1. They prevent collagen deposition and block formation of muscle fibrosis, so that a complete functional recovery can be achieved.

2003 ◽  
Vol 95 (2) ◽  
pp. 771-780 ◽  
Author(s):  
Yi-Sheng Chan ◽  
Yong Li ◽  
William Foster ◽  
Takashi Horaguchi ◽  
George Somogyi ◽  
...  

Muscle injuries are very common in traumatology and sports medicine. Although muscle tissue can regenerate postinjury, the healing process is slow and often incomplete; complete recovery after skeletal muscle injury is hindered by fibrosis. Our studies have shown that decreased fibrosis could improve muscle healing. Suramin has been found to inhibit transforming growth factor (TGF)-β1 expression by competitively binding to the growth factor receptor. We conducted a series of tests to determine the antifibrotic effects of suramin on muscle laceration injuries. Our results demonstrate that suramin (50 μg/ml) can effectively decrease fibroblast proliferation and fibrotic-protein expression (α-smooth muscle actin) in vitro. In vivo, direct injection of suramin (2.5 mg) into injured murine muscle resulted in effective inhibition of muscle fibrosis and enhanced muscle regeneration, which led to efficient functional muscle recovery. These results support our hypothesis that prevention of fibrosis could enhance muscle regeneration, thereby facilitating more efficient muscle healing. This study could significantly contribute to the development of strategies to promote efficient muscle healing and functional recovery.


2005 ◽  
Vol 33 (12) ◽  
pp. 1816-1824 ◽  
Author(s):  
Shinichi Negishi ◽  
Yong Li ◽  
Arvydas Usas ◽  
Freddie H. Fu ◽  
Johnny Huard

Background Injured skeletal muscle can repair itself via spontaneous regeneration; however, the overproduction of extracellular matrix and excessive collagen deposition lead to fibrosis. Neutralization of the effect of transforming growth factor-β1, a key fibrotic cytokine, on myogenic cell differentiation after muscle injury can prevent fibrosis, enhance muscle regeneration, and thereby improve the functional recovery of injured muscle. Hypothesis The hormone relaxin, a member of the family of insulin-like growth factors, can act as an antifibrosis agent and improve the healing of injured muscle. Study Design Controlled laboratory study. Methods In vitro: Myoblasts (C2C12 cells) and myofibroblasts (transforming growth factor-β1-transfected myoblasts) were incubated with relaxin, and cell growth and differentiation were examined. Myogenic and fibrotic protein expression was determined by Western blot analysis. In vivo: Relaxin was injected intramuscularly at different time points after laceration injury. Skeletal muscle healing was evaluated via histologic, immunohistochemical, and physiologic tests. Results Relaxin treatment resulted in a dose-dependent decrease in myofibroblast proliferation, down-regulated expression of the fibrotic protein α-smooth muscle actin, and promoted the proliferation and differentiation of myoblasts in vitro. Relaxin therapy enhanced muscle regeneration, reduced fibrosis, and improved injured muscle strength in vivo. Conclusion Administration of relaxin can significantly improve skeletal muscle healing. Clinical Relevance These findings may facilitate the development of techniques to eliminate fibrosis, enhance muscle regeneration, and improve functional recovery after muscle injuries.


Medicina ◽  
2019 ◽  
Vol 55 (5) ◽  
pp. 141 ◽  
Author(s):  
Alexandru Florian Grecu ◽  
Lucien Reclaru ◽  
Lavinia Cosmina Ardelean ◽  
Oliviu Nica ◽  
Eduard Mihai Ciucă ◽  
...  

New therapies that accelerate musculoskeletal tissue recovery are highly desirable. Platelet-rich fibrin (PRF) is a leukocyte- and platelet-rich fibrin biomaterial that acts as a binding site for both platelets and growth factors. Through increasing the local concentration of growth factors at specific tissues, PRF promotes tissue regeneration. PRF has been frequently used in combination with bone graft materials to reduce healing times and promote bone regeneration during maxillofacial surgery. However, its benefits during muscle repair and recovery are less well-documented. Here, we perform a narrative review on PRF therapies and muscle injuries to ascertain its beneficial effects. We reviewed the factors that contribute to the biological activity of PRF and the published pre-clinical and clinical evidence to support its emerging use in musculoskeletal therapy. We include in vitro studies, in vivo animal studies and clinical articles highlighting both the success and failures of PRF treatment. PRF can promote the healing process when used in a range of orthopaedic and sports-related injuries. These include cartilage repair, rotator cuff surgery and anterior cruciate ligament surgery. However, conflicting data for these benefits have been reported, most likely due to inconsistencies in both PRF preparation protocols and dosing regimens. Despite this, the literature generally supports the use of PRF as a beneficial adjuvant for a range of chronic muscle, tendon, bone or other soft tissue injuries. Further clinical trials to confirm these benefits require consistency in PRF preparation and the classification of a successful clinical outcome to fully harness its potential.


2006 ◽  
Vol 101 (4) ◽  
pp. 1215-1221 ◽  
Author(s):  
Wei Shen ◽  
Victor Prisk ◽  
Yong Li ◽  
William Foster ◽  
Johnny Huard

Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used to treat skeletal muscle injury. However, studies have shown that NSAIDs may be detrimental to the healing process. Mediated by prostaglandin F2α (PGF2α) and prostaglandin E2 (PGE2), the cycloxygenase-2 (COX-2) pathway plays an important role in muscle healing. We hypothesize that the COX-2 pathway is important for the fusion of muscle cells and the regeneration of injured muscle. For the in vitro experiments, we isolated myogenic precursor cells from wild-type (Wt) and COX-2 gene-deficient (COX-2−/−) mice and examined the effect of PGE2 and PGF2α on cell fusion. For the in vivo experiments, we created laceration injury on the tibialis anterior (TA) muscles of Wt and COX-2−/− mice. Five and 14 days after injury, we examined the TA muscles histologically and functionally. We found that the secondary fusion between nascent myotubes and myogenic precursor cells isolated from COX-2−/− mice was severely compromised compared with that of Wt controls but was restored by the addition of PGF2α or, to a lesser extent, PGE2 to the culture. Histological and functional assessments of the TA muscles in COX-2−/− mice revealed decreased regeneration relative to that observed in the Wt mice. The findings reported here demonstrate that the COX-2 pathway plays an important role in muscle healing and that prostaglandins are key mediators of the COX-2 pathway. It suggests that the decision to use NSAIDs to treat muscle injuries warrants critical evaluation because NSAIDs might impair muscle healing by inhibiting the fusion of myogenic precursor cells.


2021 ◽  
Vol 12 (2) ◽  
pp. 26-28
Author(s):  
Filipe Cabral ◽  
◽  
Pedro Barata ◽  

Muscle injuries are very common in sports medicine. Frequently the muscle repair process ends in the formation of a fibrotic scar, that not only limits the complete functional recovery, but also increases the likelihood of injury recurrence. TGF-β1 is the main profibrogenic factor involved in this healing process. By blocking its activity, Losartan has proven it efficacy in reducing fibrosis and increasing regenerative and functional capacity post muscle injury. Therefore, its use should be considered as an alternative therapeutic for this kind of injuries.


2007 ◽  
Vol 293 (1) ◽  
pp. C75-C86 ◽  
Author(s):  
Shizuya Saika ◽  
Osamu Yamanaka ◽  
Yuka Okada ◽  
Takeshi Miyamoto ◽  
Ai Kitano ◽  
...  

Wound healing involves both local cells and inflammatory cells. Alkali burn of ocular surface tissue is a serious clinical problem often leading to permanent visual impairment resulting from ulceration, scarring and neovascularization during healing. Behaviors of corneal cells and inflammatory cells are orchestrated by growth factor signaling networks that have not been fully uncovered. Here we showed that adenoviral gene introduction of peroxisome proliferator-activated receptor-γ (PPARγ) inhibits activation of ocular fibroblasts and macrophages in vitro and also induced anti-inflammatory and anti-fibrogenic responses in an alkali-burned mouse cornea. PPARγ overexpression suppressed upregulation of inflammation/scarring-related growth factors and matrix metalloproteinases (MMPs) in macrophages. It also suppressed expression of such growth factors and collagen Iα2 and myofibroblast generation upon exposure to TGFβ1. Exogenous PPARγ did not alter phosphorylation of Smad2, but inhibited its nuclear translocation. PPARγ overexpression enhanced proliferation of corneal epithelial cells, but not of fibroblasts in vitro. Epithelial cell expression of MMP-2/-9 and TGFβ1 and its migration were suppressed by PPARγ overexpression. In vivo experiments showed that PPARγ gene introduction suppressed monocytes/macrophages invasion and suppressed the generation of myofibroblasts, as well as upregulation of cytokines/growth factors and MMPs in a healing cornea. In vivo re-epitheliazation with basement membrane reconstruction in the healing, burned, cornea was accelerated by PPARγ-Ad expression, although PPARγ overexpression was considered to be unfavorable for cell migration. Together, these data suggest that overexpression of PPARγ may represent an effective new strategy for treatment of ocular surface burns.


1998 ◽  
Vol 530 ◽  
Author(s):  
Y. Tabata ◽  
M. Yamamoto ◽  
Y. Ikada

AbstractA biodegradable hydrogel was prepared by glutaraldehyde crosslinking of acidic gelatin with an isoelectric point (IEP) of 5.0 as a carrier to release basic growth factors on the basis of polyion complexation. Basic fibroblast growth factor (bFGF), transforming growth factor β1 (TGF-β1), and bone morphogenetic protein-2 (BMP-2) were sorbed from their aqueous solution into the dried gelatin hydrogels to prepare respective growth factor-incorporating hydrogels. Under an in vitro non-degradation condition, approximately 20 % of incorporated bFGF and TGF-β1 was released from the hydrogels within initial 40 min, followed by no further release, whereas a large initial release of BMP-2 was observed. After subcutaneous implantation of the gelatin hydrogels incorporating 125I-labeled growth factor in the mouse back, the remaining radioactivity was measured to estimate the in vivo release profile of growth factors. Incorporation into gelatin hydrogels enabled bFGF and TGF-β1 to retain in the body for about 15 days and the retention period well correlated with that of the gelatin hydrogel. Taken together, it is likely that the growth factors ionically complexed with acidic gelatin were released in vivo as a result of hydrogel biodegradation. On the contrary, basic BMP-2 did not ionically interact with acidic gelatin, resulting in no sustained released by the present biodegradable carrier system.


2015 ◽  
Vol 2015 ◽  
pp. 1-6 ◽  
Author(s):  
Antonio Crescibene ◽  
Marcello Napolitano ◽  
Raffaella Sbano ◽  
Enrico Costabile ◽  
Hesham Almolla

Achilles tendinopathy and patellar tendinopathy are among the most frequent diagnoses in sports medicine. Therapeutic treatment of the disease is difficult, particularly in chronic cases. In literature, several studies suggest the employment of Platelet-Rich Plasma as a therapeutic alternative in tendinopathies. The choice of employing this method is based on the activity of growth factors contained in platelets which activate, amplify, and optimize the healing process. We selected 14 patients affected by Achilles tendinopathy and 7 patients affected by patellar tendinopathy, with a two-year final follow-up. These patients underwent a cycle of three tendinous infiltrations, after clinical and instrumental evaluation carried out by means of specific questionnaires and repeated ultrasound scans. Ultrasound scans of 18 patients showed signs of reduction in insertional irregularities. The result is confirmed by complete functional recovery of the patients, with painful symptomatology disappearing. The patients showed a clear pain reduction, along with an enhanced VISA score after the 24-month follow-up, equal to 84.2 points on a scale of 0 to 100. In conclusion, the present study provides evidence to suggest that PRP infiltration is a valid option to patients with chronic tendinopathy who did not benefit from other treatments.


1999 ◽  
Vol 277 (2) ◽  
pp. C320-C329 ◽  
Author(s):  
Deepa Thaloor ◽  
Kristy J. Miller ◽  
Jonathan Gephart ◽  
Patrick O. Mitchell ◽  
Grace K. Pavlath

Skeletal muscle is often the site of tissue injury due to trauma, disease, developmental defects or surgery. Yet, to date, no effective treatment is available to stimulate the repair of skeletal muscle. We show that the kinetics and extent of muscle regeneration in vivo after trauma are greatly enhanced following systemic administration of curcumin, a pharmacological inhibitor of the transcription factor NF-κB. Biochemical and histological analyses indicate an effect of curcumin after only 4 days of daily intraperitoneal injection compared with controls that require >2 wk to restore normal tissue architecture. Curcumin can act directly on cultured muscle precursor cells to stimulate both cell proliferation and differentiation under appropriate conditions. Other pharmacological and genetic inhibitors of NF-κB also stimulate muscle differentiation in vitro. Inhibition of NF-κB-mediated transcription was confirmed using reporter gene assays. We conclude that NF-κB exerts a role in regulating myogenesis and that modulation of NF-κB activity within muscle tissue is beneficial for muscle repair. The striking effects of curcumin on myogenesis suggest therapeutic applications for treating muscle injuries.


2000 ◽  
Vol 04 (04) ◽  
pp. 265-277 ◽  
Author(s):  
Chang Woo Lee ◽  
Kazumasa Fukushima ◽  
Arvydas Usas ◽  
Lin Xin ◽  
Dalip Pelinkovic ◽  
...  

Muscle laceration is a challenging problem in traumatology and is common in sports injuries, with functional recovery remaining slow and incomplete. Even though muscles retain their ability to regenerate after injury, muscles' healing process after such injuries has been found to be very slow and often leads to incomplete muscle recovery. Growth factors may have a role in enhancing recovery. Our previous study showed that IGF-1, β-FGF and NGF can improve myoblast proliferation and differentiation in vitro. We then investigated whether the delivery of IGF-1 would improve muscle healing after injuries. We observed that muscle regeneration was enhanced in lacerated muscles treated with IGF-1 protein, which consequently led to an improvement in muscle healing. However, the rapid clearance and short biological half-lives of these proteins may have limited the success of this approach. We then investigated the efficiency of gene therapy based on adenovirus to deliver a stable expression of the growth factor IGF-1. Although a slight improvement in the healing process occurred in the muscle injected with adenovirus (AIGF), the combination of myoblast transplantation and gene therapy with the ex vivo approach further improved the healing process. The injection of normal myoblasts into the injured muscle led to the best improvement of muscle healing at two weeks post-injection. Implantation of normal minced muscle into mdx mice was also capable of improving muscle healing at 2–4 weeks post-implantation. These studies will further our understanding of muscle healing post-injury and help in the development of strategies to promote efficient muscle healing and complete functional recovery after common muscle injuries.


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