Platelet-Rich Plasma Inhibits Mechanically Induced Injury in Chondrocytes Xuetao Xie, M.D., Ph.D., Veronica Ulici, Ph.D., Peter G. Alexander, Ph.D., Yangzi Jiang, Ph.D., Changqing Zhang, M.D., Ph.D., and Rocky S. Tuan, Ph.D. Purpose: To investigate the effect of platelet-rich plasma (PRP) on mechanically injured chondrocytes. Methods: PRP from bovine whole blood was activated to prepare platelet-rich plasma releasate (PRPr). Bovine articular chondrocytes were subjected to 16%, 0.5-Hz biaxial cyclic tensile strain (CTS) for 48 hours and cultured for another 24 hours without cell stretching as an in vitro model of mechanically injured chondrocytes. Culture medium in the 3 PRP- and CTS-treated groups was supplemented with 10% PRPr at the start of CTS, after 24 hours of CTS, and after 48 hours of CTS, respectively. Gene expression levels of type II collagen, aggrecan, matrix metalloproteinase (MMP) 3, MMP-13, inducible nitric oxide synthase, and cyclooxygenase 2 were quantitatively evaluated. Changes in the content of nitric oxide (NO), prostaglandin E2 (PGE 2 ), MMP-3, and tissue inhibitor of metalloproteinase 1 in the culture medium were also measured. Results: PRPr increased type II collagen and aggrecan messenger RNA expression; diminished CTS-dependent up-regulation of MMP-3, inducible nitric oxide synthase, and cyclooxygenase 2 gene expression; and reduced CTS-induced overproduction of NO and PGE 2 when PRPr was applied early at the start of CTS. The addition of PRPr after 24 hours of CTS only inhibited MMP-3 gene up-regulation and the increase of NO and PGE 2 induced by CTS. These changes were not observed when PRPr was sup- plemented after 48 hours of CTS. PRPr mitigated the increased MMP-3 production and decreased tissue inhibitor of met- alloproteinase 1 secretion resulting from CTS in a time-dependent manner. Conclusions: PRP treatment ameliorated multiple CTS-mediated catabolic and inflammatory responses in chondrocytes. More beneficial effects were observed with early PRP application. Clinical Relevance: Intra-articular PRP injections at the beginning of strenuous exercises may be used to protect chondrocytes from mechanical injury, thus preventing joints from increased wear. C artilage homeostasis is a requirement of healthy joints. As the singular cellular component of articular cartilage, chondrocytes are responsible for the maintenance of dynamic cartilage metabolism in a low-turnover state. Mechanical damage to articular cartilage, such as in sports or recreational activities, may transiently disrupt the balance between the anabolic and catabolic states. 1 The inability of chondrocytes to tolerate this stress will result in inhibition of extracel- lular matrix (ECM) production and accumulation of mediators associated with matrix degradation, including nitric oxide (NO), prostaglandin E 2 (PGE 2 ), and matrix metalloproteinases (MMPs). 2-5 If injurious mechanical load persists and the metabolic imbalance cannot be corrected in time, progressive cartilage degeneration will likely occur. 1,6 In the past decade, platelet-rich plasma (PRP) has been frequently applied for the purpose of stimulating matrix accumulation and inhibiting cartilage degrada- tion because of abundant anabolic and anti- inflammatory cytokines in its releasate (PRPr). 7,8 Several preclinical and clinical studies have been reported with encouraging results using PRP for the treatment of osteoarthritis (OA), which is characterized by high catabolism and low anabolism of articular cartilage. 7,8 More importantly, a few randomized controlled trials have recently confirmed the effective- ness of PRP in relieving OA symptoms and improving From the Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine (X.X., V.U., P.G.A., Y.J., R.S.T.), Pittsburgh, Pennsylvania, U.S.A.; and Department of Orthopaedic Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital (X.X., C.Z.), Shanghai, China. The authors report the following potential conflict of interest or source of funding: The work was supported by the Commonwealth of Pennsylvania Department of Health and US Department of Defense (W81XWH-08-2-0032 and W81XWH-10-1-0850). X.X. receives support from China Scholarship Council. V.U. receives support from Arthritis Foundation for postdoctoral fellowship. Received April 3, 2014; accepted January 9, 2015. Address correspondence to Rocky S. Tuan, Ph.D., Center for Cellular and Molecular Engineering, Department of Orthopaedic Surgery, University of Pittsburgh School of Medicine, 450 Technology Dr, Room 221, Pittsburgh, PA 15219, U.S.A. E-mail: rst13@pitt.edu Ó 2015 by the Arthroscopy Association of North America 0749-8063/14281/$36.00 http://dx.doi.org/10.1016/j.arthro.2015.01.007 Arthroscopy: The Journal of Arthroscopic and Related Surgery, Vol -, No - (Month), 2015: pp 1-9 1