Abstract
BackgroundTo investigate if cartilage related biomarkers in synovial fluid are associated with knee cartilage status 20 years after an anterior cruciate ligament (ACL) injury.MethodsWe studied 25 patients with a complete ACL rupture without subsequent ACL reconstruction or radiographic knee OA. All had a delayed gadolinium-enhanced magnetic resonance imaging of cartilage (dGEMRIC) 20 years after the ACL injury, using the T1 transverse relaxation time in the presence of gadolinium (T1Gd) which estimates the concentration of glycosaminoglycans in hyaline cartilage. Synovial fluid samples were aspirated acutely (between 0 and 18 days) and during 1 to 5 follow up visits between 0.5 and 7.5 years after injury. We quantified synovial fluid concentrations of aggrecan (epitopes 1-F21 and ARGS), cartilage oligomeric matrix protein, matrix metalloproteinase-3 and tissue inhibitor of metalloproteinase-1 by immunoassays, and sulfated glycosaminoglycans by Alcian blue precipitation. Western blot was used for qualitative analyses of aggrecan fragments in synovial fluid and cartilage samples.ResultsWestern blot indicated that the 1-F21 epitope was located within the chondroitin sulfate 2 region of aggrecan. Linear regression analyses (adjusted for age, sex, body mass index and time between injury and sampling) showed that acute higher synovial fluid 1-F21-aggrecan concentrations were associated with shorter T1Gd values 20 years after injury, i.e. inferior cartilage quality (standardized effects between − 0.67 and − 1.0). No other statistically significant association was found between molecular biomarkers and T1Gd values.ConclusionHigher acute synovial fluid 1-F21-aggrecan concentrations in ACL injured patients, who managed to cope without ACL reconstruction and were without radiographic knee OA, were associated with inferior knee cartilage quality assessed by dGEMRIC 20 years after injury.
Highlights
To investigate if cartilage related biomarkers in synovial fluid are associated with knee cartilage status 20 years after an anterior cruciate ligament (ACL) injury
We further investigated the ratios of sulfated glycosaminoglycans (sGAG)/Cartilage oligomeric matrix protein (COMP), ARGS-aggrecan/COMP and 1F21 aggrecan/COMP as biomarkers; ratios like these have been suggested to minimize the influence of varying amounts of obtainable synovial fluid [47]
For all biomarkers measured in synovial fluid, the concentrations were higher in the acute samples compared to chronic samples (Table 2)
Summary
To investigate if cartilage related biomarkers in synovial fluid are associated with knee cartilage status 20 years after an anterior cruciate ligament (ACL) injury. Post-traumatic osteoarthritis (OA) is common after an anterior cruciate ligament (ACL) injury and is manifested by radiographic structural knee joint changes with osteophytes and decreased cartilage height, and with patients experiencing knee pain and stiffness [1,2,3,4,5,6]. The ACL injury with cartilage damage triggers an immediate inflammatory response which acts in combination with an abnormal long-term mechanical loading of the injured knee believed to generate post-traumatic OA [11,12,13]. The dGEMRIC technique has proved to have a prognostic value for OA development [29,30,31]
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