title: Intraarticular Matrix Metalloproteinases and Aggrecan Degradation Are Elevated After Articular Fracture.
abstract: BACKGROUND
  Posttraumatic osteoarthritis (OA) is a variant of OA that can develop after articular injury. Although the mechanism(s) of posttraumatic OA are uncertain, the presence and impact of postinjury proteolytic enzymes on articular cartilage remain unknown. To our knowledge, there are no studies that evaluate the presence of matrix metalloproteinases (MMPs) or aggrecan degradation after articular fracture.
  
  
  OBJECTIVE
  (1) Are MMP concentrations and aggrecan degradation elevated after intraarticular fracture? (2) Are MMP concentrations and aggrecan degradation greater in high-energy injuries compared with low-energy injuries? (3) Do the concentrations of these biomarkers remain elevated at a secondary aspiration?
  
  
  METHODS
  Between December 2011 and June 2013, we prospectively enrolled patients older than 18 years of age with acute tibial plateau fracture. Exclusion criteria included age older than 60 years, preexisting knee OA, injury greater than 24 hours before evaluation, contralateral knee injury, history of autoimmune disease, open fracture, and non-English-speaking patients. During the enrollment period, we enrolled 45 of the 91 (49%) tibial plateau fractures treated at our facility. Knee synovial fluid aspirations were obtained from both the injured and uninjured knees; two patients received aspirations in the emergency department and the remaining patients received aspirations in the operating room. Twenty patients who underwent spanning external fixator followed by definitive fixation were aspirated during both surgical procedures. MMP-1, -2, -3, -7, -9, -10, -12, and -13 concentrations were quantified using multiplex assays. Aggrecan degradation was quantified using sandwich enzyme-linked immunosorbent assay.
  
  
  RESULTS
  There were higher concentrations of MMP-1 (3.89 ng/mL [95% confidence interval {CI}, 2.37-6.37] versus 0.37 ng/mL [95% CI, 0.23-0.61], p < 0.001), MMP-3 (457.35 ng/mL [95% CI, 274.5-762.01] versus 129.17 ng/mL [95% CI, 77.01-216.66], p < 0.001), MMP-9 (6.52 ng/mL [95% CI, 3.86-11.03] versus 0.96 ng/mL [95% CI, 0.56-1.64], p < 0.001), MMP-10 (0.52 ng/mL [95% CI, 0.40-0.69] versus 0.23 ng/mL [95% CI, 0.17-0.30], p < 0.001), and MMP-12 (0.18 ng/mL [95% CI, 0.14-0.23] versus 0.10 ng/mL [95% CI, 0.0.081-0.14], p = 0.005) in injured knees compared with uninjured knees. There was not a detectable difference in MMP concentrations or aggrecan degradation between high- and low-energy injuries. MMP-1 (53.25 versus 3.89 ng/mL, p < 0.001), MMP-2 (76.04 versus 0.37 ng/mL, p < 0.001), MMP-3 (1250.62 versus 457.35 ng/mL, p = 0.002), MMP-12 (1.37 versus 0.18, p < 0.001), MMP-13 (0.98 versus 0.032 ng/mL, p < 0.001), and aggrecan degradation (0.58 versus 0.053, p < 0.001) were increased at the second procedure (mean, 9.5 days; range, 3-21 days) as compared with the initial procedure.
  
  
  CONCLUSIONS
  Because MMPs and aggrecan degradation are elevated after articular fracture, future studies are necessary to evaluate the impact of elevated MMPs and aggrecan degradation on human articular cartilage.
  
  
  CONCLUSIONS
  If further clinical followup can demonstrate a relationship between posttraumatic OA and elevated MMPs and aggrecan degradation, they may provide potential for therapeutic targets to prevent or delay the destruction of the joint. Additionally, these markers may offer prognostic information for patients.
authors.affiliation: Department of Orthopaedics, University of Utah School of Medicine, 590 Wakara Way, Salt Lake City, UT, 84108, USA.
authors.forename: Justin M
authors.initials: JM
authors.lastname: Haller
authors.forename: Craig A
authors.initials: CA
authors.lastname: Swearingen
authors.forename: Deveree
authors.initials: D
authors.lastname: Partridge
authors.forename: Molly
authors.initials: M
authors.lastname: McFadden
authors.forename: Kannan
authors.initials: K
authors.lastname: Thirunavukkarasu
authors.forename: Thomas F
authors.initials: TF
authors.lastname: Higgins
mesh_terms: D000328:Adult; D053674:Aggrecans / Q000378:metabolism*; D015415:Biomarkers / Q000032:analysis; D005260:Female; D006801:Humans; D057072:Intra-Articular Fractures / Q000150:complications / Q000378:metabolism*; D007718:Knee Injuries / Q000150:complications / Q000378:metabolism*; D008297:Male; D020782:Matrix Metalloproteinases / Q000032:analysis*; D008875:Middle Aged; D010003:Osteoarthritis / Q000209:etiology / Q000378:metabolism*; D011446:Prospective Studies; D013582:Synovial Fluid / Q000737:chemistry* / Q000378:metabolism*; D055815:Young Adult
chemical_list: C508319:ACAN protein, human; D053674:Aggrecans; D015415:Biomarkers; D020782:Matrix Metalloproteinases