Abstract | BACKGROUND: Muscle contusions are a common type of muscle injury and are frequently encountered in athletes and military personnel. Although these injuries are capable of healing in most instances, incomplete functional recovery often occurs because of the development of fibrosis in the muscle. We hypothesized that a combination of platelet-rich plasma (PRP) injection and oral administration of losartan (an antifibrotic agent) could enhance muscle healing by stimulating muscle regeneration and angiogenesis and by preventing fibrosis in contusion-injured skeletal muscle. METHODS:
Contusion injuries were created in the tibialis anterior muscles of mice. Two treatments were tested, alone and in combination: 20 μL of PRP injected into the contusion site one day after injury, and 10 mg/kg/day of losartan administered beginning three days after injury and continuing until the end point of the experiment. Muscle regeneration and fibrosis development were evaluated by histological analysis, and functional recovery was measured by physiological testing. RESULTS: Muscle regeneration and muscle function were significantly promoted in the combined PRP + losartan treatment group compared with the other groups. Combined PRP + losartan treatment significantly decreased the expression of phosphorylated Smad2/3 and the development of fibrosis compared with PRP treatment alone, and it increased vascular endothelial growth factor ( VEGF) expression and the number of CD31-positive structures compared with losartan treatment alone. Follistatin, a positive regulator of muscle growth, was expressed at a higher level in the PRP + losartan group compared with the other groups. CONCLUSIONS: CLINICAL RELEVANCE: These findings could contribute to the development of biological treatments that aid in the healing of skeletal muscle after injury.
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Authors | Satoshi Terada, Shusuke Ota, Makoto Kobayashi, Tetsuo Kobayashi, Yutaka Mifune, Koji Takayama, Michelle Witt, Gianluca Vadalà, Nick Oyster, Takanobu Otsuka, Freddie H Fu, Johnny Huard |
Journal | The Journal of bone and joint surgery. American volume
(J Bone Joint Surg Am)
Vol. 95
Issue 11
Pg. 980-8
(Jun 05 2013)
ISSN: 1535-1386 [Electronic] United States |
PMID | 23780535
(Publication Type: Journal Article)
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Chemical References |
- Angiotensin II Type 1 Receptor Blockers
- Transforming Growth Factor beta1
- Losartan
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Topics |
- Angiotensin II Type 1 Receptor Blockers
(pharmacology)
- Animals
- Contusions
(drug therapy, pathology)
- Enzyme-Linked Immunosorbent Assay
- Female
- Fluorescent Antibody Technique
- Losartan
(pharmacology)
- Mice
- Mice, Inbred C57BL
- Muscle, Skeletal
(injuries, pathology)
- Platelet-Rich Plasma
(drug effects)
- Regeneration
(drug effects)
- Transforming Growth Factor beta1
(metabolism)
- Wound Healing
(drug effects)
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