Year: 2012
Type: article
Abstract: Muscle injuries are very common musculoskeletal problems in sports medicine. Although current therapies such as RICE (rest, ice, compression, and elevation) are the norm for treatment, complete functional recovery is hindered by the development of scar tissue formation. Myostatin, a negative regulator of muscle growth, has been shown to stimulate fibrosis in skeletal muscle.1 Thus, we have focused the current study on the prevention of scar tissue through the down-regulation of myostatin by suramin, an anti-fibrotic agent which is already approved by Food and Drug Administration (FDA). Using an animal (murine) model of muscle contusion, we examined, 1) whether suramin can block the effect of myostatin and promote myogenic differentiation of myoblast cells in vitro and 2) whether suramin treatment enhances muscle regeneration and reduce fibrosis by down-regulating myostatin expression in vivo. In vitro: Myoblast cells were cultured with low-serum medium containing different concentrations of myostatin (0 and 1 g/ml) and suramin (0, 1, and 25 g/ml) to induce myogenic differentiation. In vivo: The muscle contusion was made on the tibialis anterior (TA) muscle of each mouse. Two weeks after injury, different concentrations of suramin (0 and 2.5 mg) were injected intramuscularly (n=20 mice/ group). At different time points (0.5, 1, 2, 10, and 14 days after injection), mice were sacrificed and cryosections of TA muscle were analyzed histologically. In vitro: Myostatin treatment significantly inhibited the myogenic differentiation of myoblasts. However, suramin treatment significantly blocked myostatin's effects and moreover suramin treatment stimulated the fusion of myoblasts in a dose-dependent manner in the presence of myostatin. In vivo: Suramin (2.5 mg) injection demonstrated a significant increase in the number of regenerating myofibers and reduction of fibrotic area when compared with the control group (0 mg). Furthermore, suramin injection effectively inhibited the expression of myostatin in the injured muscle. Suramin improved skeletal muscle healing by enhancing regeneration and reducing fibrosis after contusion injury. Furthermore, a decrease the expression of myostatin in injured muscle treated with suramin may reveal a possible mechanism by which suramin improves skeletal muscle healing after injury. Our findings may contribute to the development of progressive therapies for muscle injury.
Authors: Hideyuki Goto, Masaaki Kobayashi, Hirotaka Iguchi, Yuko Nagaya, Takanobu Otsuka, Freddie H. Fu, Johnny Huard, Masahiro Nozaki
Language: English
Subfield: Molecular Biology
Domain: Life Sciences
Open Access status: bronze
OpenAlex ID: W2024708797