title: Platelet-rich plasma modulates the secretion of inflammatory/angiogenic proteins by inflamed tenocytes.
abstract: BACKGROUND
  Platelet-rich plasma therapies for tendinopathy appear to provide moderate pain reduction. However, the biological mechanisms behind the observed clinical effects remain poorly characterized.
  
  
  OBJECTIVE
  The purpose of this study was to explore whether platelet-rich plasma modifies the inflammatory/angiogenic status of already inflamed tenocytes by examining (1) gene expression; (2) modulation of chemokine and interleukin secretion; and (3) differences between healthy and tendinopathic tenocytes.
  
  
  METHODS
  Cells from both healthy and tendinopathic tendons were exposed to interleukin (IL)-1ß and after treated with platelet-rich plasma. Modifications in the expression of selected genes were assessed by real-time reverse transcription-polymerase chain reaction and changes in secretion of angiogenic/inflammatory molecules by enzyme-linked immunosorbent assay. Platelet-rich plasma-induced changes in tendinopathic cells were compared with normal after normalizing platelet-rich plasma data against IL-1ß status in each specific sample.
  
  
  RESULTS
  In IL-1ß-exposed cells, platelet-rich plasma downregulates expression of IL-6/CXCL-6 (mean, 0.015; 95% confidence interval [CI], 0.005-0.025; p = 0.026), IL-6R (mean, 0.61; 95% CI, 0.27-0.95; p = 0.029), and IL-8/CXCL-8 (mean, 0.02; 95% CI, 0.007-0.023; p = 0.026). Secretion of IL-6/CXCL6, 0.35 (95% CI, 0.3-0.4; p = 0.002), IL-8/CXCL8, 0.55 (95% CI, 0.5-0.7; p = 0.01), and monocyte chemoattractant protein-1/CCL2, 0.40 (95% CI, 0.2-0.6; p = 0.001) was reduced by platelet-rich plasma, whereas vascular endothelial growth factor increased by twofold, (95% CI, 1.7-2.3; p < 0.001). RANTES/CCL5 increased by10-fold (95% CI, 4-17) and hepatocyte growth factor by 21-fold (95% CI, 0.2-42) in tendinopathic and by 2.3-fold (95% CI, 2-3) and threefold (95% CI, 1-5) in normal cells (p = 0.005 for both).
  
  
  CONCLUSIONS
  Platelet-rich plasma induces an immunomodulatory and proangiogenic phenotype consistent with healing mechanisms with few differences between tendinopathic and normal cells.
  
  
  CONCLUSIONS
  Platelet-rich plasma injections in pathological and nearby tissue might help to recover tendon homeostasis.
authors: Regenerative medicine Group, Biocruces Health Research Institute, Cruces University Hospital, 48903, Barakaldo, Spain.
authors: Isabel
authors: I
authors: Andia
authors: Eva
authors: E
authors: Rubio-Azpeitia
authors: Nicola
authors: N
authors: Maffulli
mesh_terms: D042501:Angiogenic Proteins / Q000235:genetics / Q000378:metabolism*; D016022:Case-Control Studies; D002478:Cells, Cultured; D016207:Cytokines / Q000378:metabolism*; D005786:Gene Expression Regulation; D006801:Humans; D018836:Inflammation Mediators / Q000378:metabolism*; D053583:Interleukin-1beta / Q000494:pharmacology; D010641:Phenotype; D053657:Platelet-Rich Plasma / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D015398:Signal Transduction; D052256:Tendinopathy / Q000097:blood / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000628:therapy*; D013710:Tendons / Q000187:drug effects / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013997:Time Factors; D014945:Wound Healing / Q000187:drug effects
chemical_list: D042501:Angiogenic Proteins; D016207:Cytokines; D018836:Inflammation Mediators; D053583:Interleukin-1beta; D012333:RNA, Messenger