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Detecting cathepsin activity in human osteoarthritis via activity-based probes. | LitMetric

AI Article Synopsis

  • Lysosomal cathepsins have been linked to the development and severity of Osteoarthritis (OA), making their activity a potential marker for assessing the condition.
  • The study used a specific probe (ABP, GB123) to measure cathepsin B and S activity in various samples, including cultured cells and patient fluid, highlighting increased activity in OA.
  • Results indicated that cathepsin B levels rise with OA severity, while cathepsin S is more associated with joint inflammation and rheumatoid arthritis, suggesting the potential for these cathepsins as targets for early OA detection.

Article Abstract

Introduction: Lysosomal cathepsins have been reported to contribute to Osteoarthritis (OA) pathophysiology due to their increase in pro-inflammatory conditions. Given the causal role of cathepsins in OA, monitoring their specific activity could provide means for assessing OA severity. To this end, we herein sought to assess a cathepsin activity-based probe (ABP), GB123, in vitro and in vivo.

Methods: Protein levels and activity of cathepsins B and S were monitored by immunoblot analysis and GB123 labeling in cultured primary chondrocytes and conditioned media, following stimuli with tumor necrosis factor alpha (TNFα) and/or Interleukin 1 beta (IL-1β). Similarly, cathepsin activity was examined in sections of intact cartilage (IC) and degraded cartilage (DC) regions of OA. Finally, synovial fluid (SF) and serum from donors with no signs of diseases, early OA, late OA and rheumatoid arthritis (RA) patients were analyzed with GB123 to detect distinct activity levels of cathepsin B and S.

Results: Cathepsin activity in cell lysates, conditioned media explants and DC sections showed enhanced enzymatic activity of cathepsins B and S. Further histological analysis revealed that cathepsin activity was found higher in superficial zones of DC than in IC. Examining serum and SF revealed that cathepsin B is significantly elevated with OA severity in serum and SF, yet levels of cathepsin S are more correlated with synovitis and RA.

Conclusions: Based on our data, cathepsin activity monitored by ABPs correlated well with OA severity and joint inflammation, directing towards a novel etiological target for OA, which possesses significant translational potential in developing means for non-invasive detection of early signs of OA.

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Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4415352PMC
http://dx.doi.org/10.1186/s13075-015-0586-5DOI Listing

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