title: Differential Interactive Effects of Cartilage Traumatization and Blood Exposure In Vitro and In Vivo.
abstract: BACKGROUND
  Sport injuries of the knee often lead to posttraumatic arthritis. In addition to direct damage of the cartilage, trauma-associated intra-articular bleeding may cause hemarthrosis. Both blood exposure and trauma are known to induce cell death and inflammation and to enhance proteoglycan release in cartilage.
  
  
  OBJECTIVE
  Blood exposure increases chondrocyte death as well as inflammatory and degenerative processes in traumatized cartilage.
  
  
  METHODS
  Controlled laboratory study.
  
  
  METHODS
  Human macroscopically intact osteoarthritic (OA) cartilage explants were impacted by a drop-tower system (0.59 J) and cultivated with or without 10% blood. Interactive effects were studied concerning cell survival, gene expression, and the release of mediators over 24 hours and 96 hours. To evaluate the effects of trauma and hemarthrosis in vivo, a newly established blunt cartilage trauma model in the rabbit was used. Treatment of the knee joints of mature New Zealand White rabbits consisted of the following groups: control (C), arthrotomy (A), arthrotomy with cartilage trauma (AT; 1.0 J), and arthrotomy with cartilage trauma and blood injection (ATH). After 1 and 12 weeks, inflammatory mediators in the synovial fluid and histological changes of the cartilage were determined, and immunohistological staining was performed.
  
  
  RESULTS
  The in vitro studies revealed a significant additional or synergistic effect of blood exposure on trauma-induced chondrocyte death, interleukin (IL)-1β and prostaglandin-E2 (PGE2) release, and matrix metalloproteinase (MMP)/pro-MMP level. Singular arthrotomy in vivo induced a temporary inflammation. Histologically, cartilage trauma caused significant OA changes that were not aggravated by an additional hemarthrosis. Trauma led to a persistent deposition of terminal complement complex (TCC), being enhanced by hemarthrosis. However, trauma-induced formation of osteophytes and arthrotomy-induced elevation of tumor necrosis factor-α release were reduced by hemarthrosis.
  
  
  CONCLUSIONS
  While blood exposure clearly aggravated trauma-induced OA processes in the in vitro model, a singular blood injection revealed heterogeneous effects in vivo, enhancing TCC deposition but reducing trauma-induced osteophyte formation while the histological score of traumatized cartilage was not further impaired.
  
  
  CONCLUSIONS
  The results of this study indicate that a singular, limited bleeding event might not exacerbate early trauma-induced cartilage degeneration in joint injuries. An early removal of intra-articular blood may not prevent the final resulting cartilage damage.
authors.affiliation: Division for Biochemistry of Joint and Connective Tissue Diseases, Department of Orthopedics, University of Ulm, Ulm, Germany.
authors.forename: Helga
authors.initials: H
authors.lastname: Joos
authors.affiliation: Department of Orthopedics, University of Ulm, Ulm, Germany.
authors.forename: Frank
authors.initials: F
authors.lastname: Leucht
authors.affiliation: Division for Biochemistry of Joint and Connective Tissue Diseases, Department of Orthopedics, University of Ulm, Ulm, Germany.
authors.forename: Jana
authors.initials: J
authors.lastname: Riegger
authors.affiliation: Division for Biochemistry of Joint and Connective Tissue Diseases, Department of Orthopedics, University of Ulm, Ulm, Germany.
authors.forename: Cathrin
authors.initials: C
authors.lastname: Hogrefe
authors.affiliation: Division for Biochemistry of Joint and Connective Tissue Diseases, Department of Orthopedics, University of Ulm, Ulm, Germany.
authors.forename: Jörg
authors.initials: J
authors.lastname: Fiedler
authors.affiliation: Institute of Orthopedic Research and Biomechanics, University of Ulm, Ulm, Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Dürselen
authors.affiliation: Department of Orthopedics, University of Ulm, Ulm, Germany.
authors.forename: Heiko
authors.initials: H
authors.lastname: Reichel
authors.affiliation: Institute of Orthopedic Research and Biomechanics, University of Ulm, Ulm, Germany.
authors.forename: Anita
authors.initials: A
authors.lastname: Ignatius
authors.affiliation: Division for Biochemistry of Joint and Connective Tissue Diseases, Department of Orthopedics, University of Ulm, Ulm, Germany rolf.brenner@uni-ulm.de.
authors.forename: Rolf E
authors.initials: RE
authors.lastname: Brenner
mesh_terms: D000368:Aged; D000818:Animals; D002358:Cartilage, Articular / Q000293:injuries*; D016923:Cell Death; D002470:Cell Survival; D019902:Chondrocytes / Q000473:pathology*; D015232:Dinoprostone / Q000378:metabolism; D005260:Female; D015870:Gene Expression; D006395:Hemarthrosis / Q000378:metabolism; D006801:Humans; D007249:Inflammation / Q000473:pathology*; D053583:Interleukin-1beta / Q000378:metabolism; D007719:Knee Joint / Q000473:pathology*; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D008875:Middle Aged; D011509:Proteoglycans / Q000378:metabolism; D011817:Rabbits; D013582:Synovial Fluid / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D053583:Interleukin-1beta; D011509:Proteoglycans; D014409:Tumor Necrosis Factor-alpha; D020782:Matrix Metalloproteinases; D015232:Dinoprostone
keywords: blood; cartilage; hemarthrosis; posttraumatic arthritis; trauma