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.Questions/purposes (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-3The institution of one or more of the authors (JMH, TFH) has received peer-reviewed research grant funding from the Orthopedic Trauma Association, LS Peery Foundation, and AO North America for this project. One of the authors certifies that he (TFH), or a member of his immediate family, has signed an agreement with DePuy Synthes (Warsaw, IN, USA) for consulting activities not related to the current study, and has not received payments or benefits, during the study period. One or more of the authors (CAS, KT) are employed at Eli Lilly (Indianapolis, IN, USA). All ICMJE Conflict of Interest Forms for authors and Clinical Orthopaedics and Related Research1 editors and board members are on file with the publication and can be viewed on request. Clinical Orthopaedics and Related Research1 neither advocates nor endorses the use of any treatment, drug, or device. Readers are encouraged to always seek additional information, including FDAapproval status, of any drug or device prior to clinical use. Each author certifies that his or her institution approved or waived approval for the reporting of this investigation and that all inves...

Inflammatory cytokine response is greater in acute tibial plafond fractures than acute tibial plateau fractures

“…However, MMP‐13 significantly increased from initial injury to the second aspiration and it was significantly elevated in the injured ankle compared to the uninjured ankle at the second aspiration. This is consistent with prior studies that suggest that MMP‐13 may rely on other factors for upregulation . Targeting the cytokines and chemokines that are involved in MMP‐13 upregulation may offer therapeutic strategies to limit MMP‐13 accumulation after injury.…”

“…This is consistent with prior studies that suggest that MMP-13 may rely on other factors for upregulation. 4,15,16 Targeting the cytokines and chemokines that are involved in MMP-13 upregulation may offer therapeutic strategies to limit MMP-13 accumulation after injury.…”

“…The patients that formed the tibial plateau fracture group have already been discussed in greater detail. 3,4 Briefly, the tibial plateau patients were enrolled during a similar study period using the same inclusion/exclusion criteria as the plafond fracture patients. The synovial fluid samples were obtained, processed, and stored using the same methods.…”

“…The post‐traumatic inflammatory response has been proposed as playing a role in the development of PTOA . Prior studies have demonstrated an elevated inflammatory response following acute tibial plateau fracture . However, the rate of PTOA following tibial plateau fractures is not as high as tibial plafond fractures .…”

“…2 Prior studies have demonstrated an elevated inflammatory response following acute tibial plateau fracture. 3,4 However, the rate of PTOA following tibial plateau fractures is not as high as tibial plafond fractures. 5 The purpose of this study was to evaluate the presence of inflammatory cytokines and matrix metalloproteinases (MMPs) following acute plafond fractures, and to compare this inflammatory response to the inflammatory response following acute tibial plateau fractures.…”