Upregulation of Matrix Degrading Enzymes and Lubricin in the Pathogenesis of Joint Disease Requiring Arthroplasty

Abstract

IntroductionThe prevalence of total knee and hip arthroplasty (TKA and THA) has been increasing; it is projected that TKA and THA procedures will increase to over 4 million procedures by 2030. Since TKA and THA are performed on individuals who experience joint degeneration, it is of interest to study the matrix degrading enzymes (MDE) such as elastase, collagenase‐1, and heparanase. Lubricin is a synovial/joint glycoprotein‐detectable in circulation‐ that plays a vital role in joint mobility by reducing friction in the joint and may have matrix‐stabilizing properties. Previous studies have investigated MDEs in TKA and THA patients, particularly involving prosthesis loosening, yet the role of lubricin is unclear. Simultaneous MDE and lubricin measurement may provide insight on the role of lubricin and these MDEs in the pathogenesis of joint diseases.MethodsBlood samples were obtained from patients undergoing THA or TKA procedures as de‐identified samples day one pre‐op and day one post‐op. Patient blood samples were collected in 3.2% sodium citrate to obtain plasma. Patient and control plasma samples were stored at −80°C. Plasma samples were analyzed utilizing commercially available ELISA kits for elastase, collagenase‐1, heparanase, and lubricin.ResultsIn comparison to normal samples, collagenase and elastase levels were significantly higher in the pre‐op samples (p<0.0001). However heparanase levels were not significantly different between the normal and patient group (p<0.748). On post‐op day 1, a further increase in the collagenase and elastase levels were noted again (p<0.0001). No further increase was evident in the heparanase level. Lubricin levels were markedly higher in the patient groups in comparison to the normal (p<0.0001). On post‐op day 1 marked enhancement of circulating lubricin was noted.DiscussionThe increased levels of lubricin suggest that, joint matrix deteriorates during joint degeneration damaging the capsule allows the joint fluid into systemic circulation. This may be the primary cause of the increased level of lubricin in circulation. Since DJD is a systemic disease with multiple pathogenic factors, it may result in the upregulation of collagenase and elastase. The role of heparanase remains unclear and requires further exploration. It is likely that lubricin may regulate the functional behavior of matrix degrading proteins. These studies also suggest that beside matrix degrading proteins, lubricin may also have a prognostic role in DJD.