Use of an antifibrotic agent improves the effect of platelet-rich plasma on muscle healing after injury

Terada, S and Ota, S and Kobayashi, M and Kobayashi, T and Mifune, Y and Takayama, K and Witt, M and Vadalà, G and Oyster, N and Otsuka, T and Fu, FH and Huard, J (2013) Use of an antifibrotic agent improves the effect of platelet-rich plasma on muscle healing after injury. Journal of Bone and Joint Surgery - Series A, 95 (11). 980 - 988. ISSN 0021-9355

	PDF Restricted to University of Pittsburgh users only Available under License : See the attached license file. Download (1MB) | Request a Copy
	Plain Text (licence) Available under License : See the attached license file. Download (1kB)

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 anteriormuscles 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: PRP + losartan combinatorial therapy improved overall skeletal muscle healing after muscle contusion injury by enhancing angiogenesis and follistatin expression and by reducing the expression of phosphorylated Smad2/3 and the development of fibrosis. These results suggest that blocking the expression of transforming growth factor (TGF)-β1 with losartan improves the effect of PRP therapy on muscle healing after a contusion injury. Clinical Relevance: These findings could contribute to the development of biological treatments that aid in the healing of skeletal muscle after injury. Copyright © 2013 by The Journal of Bone and Joint Surgery, Incorporated.

---

Share

Citation/Export:	Select format... Citation - Text Citation - HTML Endnote BibTex Dublin Core OpenURL MARC (ISO 2709) METS MODS EP3 XML Reference Manager Refer
Social Networking:	Share |

---

Details

Item Type:	Article
Status:	Published
Creators/Authors:	Creators Email Pitt Username ORCID Terada, S Ota, S Kobayashi, M Kobayashi, T Mifune, Y Takayama, K Witt, M Vadalà, G Oyster, N Otsuka, T Fu, FH ffu@pitt.edu FFU Huard, J
Centers:	Other Centers, Institutes, Offices, or Units > Stem Cell Research Center
Date:	5 June 2013
Date Type:	Publication
Journal or Publication Title:	Journal of Bone and Joint Surgery - Series A
Volume:	95
Number:	11
Page Range:	980 - 988
DOI or Unique Handle:	10.2106/jbjs.l.00266
Schools and Programs:	School of Medicine > Orthopaedic Surgery
Refereed:	Yes
ISSN:	0021-9355
PubMed ID:	23780535
Date Deposited:	04 Apr 2014 15:51
Last Modified:	03 Feb 2019 10:55
URI:	http://d-scholarship.pitt.edu/id/eprint/20804

---

Metrics

Monthly Views for the past 3 years

Plum Analytics

Altmetric.com

---

Actions (login required)

View Item