Distinct Effects of Platelet-Rich Plasma and BMP13 on Rotator Cuff Tendon Injury Healing in a Rat Model

富血小板血浆 医学 生长因子 肌腱 细胞外基质 伤口愈合 转化生长因子 纤维连接蛋白 肌腱病 血管内皮生长因子 基因表达 病理 细胞生物学 血小板 外科 内科学 生物 基因 血管内皮生长因子受体 受体 生物化学
作者
Joseph D. Lamplot,Michael E. Angeline,Jovito Angeles,Maureen Beederman,Eric R. Wagner,Farbod Rastegar,Bryan L. Scott,Christian Skjong,Daniel P. Mass,Richard W. Kang,Sherwin S.W. Ho,Lewis L. Shi
出处
期刊:American Journal of Sports Medicine [SAGE]
卷期号:42 (12): 2877-2887 被引量:46
标识
DOI:10.1177/0363546514547171
摘要

Background: Although platelet-rich plasma (PRP) is used clinically to augment tendon healing, bone morphogenetic protein–13 (BMP13) may provide a better therapeutic avenue to improve early tendon healing and repair. Hypothesis: Exogenous expression of BMP13 in tenocytes will up-regulate genes involved in tendon healing. Direct delivery of adenovirus-mediated BMP13 (AdBMP13) into the injured rat supraspinatus tendon will increase biomechanical properties. Study Design: Controlled laboratory study. Methods: Exogenous expression of BMP13 and the major growth factors in PRP (transforming growth factor–β1 [TGF-β1], vascular endothelial growth factor–A [VEGF-A], and platelet-derived growth factor–BB [PDGF-BB]) was accomplished by using recombinant adenoviral vectors. The expression of tendon- and matrix-associated genes in growth factor–treated tenocytes was analyzed by use of semiquantitative reverse-transcription polymerase chain reaction. A total of 32 rats with supraspinatus defect were divided into 4 groups and injected with adenovirus-containing green fluorescent protein (AdGFP; negative control), PRP, AdBMP13, or PRP+AdBMP13. All rats were sacrificed at 2 weeks after surgery, and tendons were harvested for biomechanical testing and histologic analysis. Results: BMP13 up-regulated type III collagen expression compared with AdGFP control and PRP growth factors ( P < .01). BMP13 and PRP growth factors each up-regulated fibronectin expression ( P < .01). There was an increase in stress to failure in each of the 3 treatment groups ( P < .05 for PRP; P < .01 for AdBMP13 or PRP+AdBMP13) compared with AdGFP control. AdBMP13 demonstrated higher stress to failure than did the PRPs ( P < .01). The addition of PRP did not increase the BMP13-enhanced stress to failure or stiffness. The biomechanical results were further supported by histologic analysis of the retrieved samples. Conclusion: Exogenous expression of BMP13 enhances tendon healing more effectively than PRP as assessed by tendon- and matrix-associated gene expression, biomechanical testing, and histologic analysis. Clinical Relevance: While PRP is used in the clinical setting, BMP13 may be explored as a superior biofactor to improve rotator cuff tendon healing and reduce the incidence of retears.
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