Plasma and Joint Fluid Glypican-3 Are Inversely Correlated with the Severity of Knee Osteoarthritis

Cartilage. 2021 Oct;12(4):505-511. doi: 10.1177/1947603519841679. Epub 2019 Apr 4.


Objective: Glypican-3 possesses a possible action in regulation of bone growth and development implicated in osteoarthritis (OA) pathology. Therefore, this study aimed to investigate glypican-3 in plasma and synovial fluid of knee OA patients and to determine the possible association between glypican-3 levels and radiographic severity.

Design: A total of 80 knee OA patients and 80 healthy controls were recruited. Glypican-3 levels in plasma and synovial fluid were measured using enzyme-linked immunosorbent assay. The severity of knee OA was assessed by radiographic grading according to the Kellgren-Lawrence classification. Relative mRNA expression of glypican-3 in 10 inflamed synovial tissues from OA patients and 10 noninflamed synovial controls was quantified using real-time polymerase chain reaction.

Results: Plasma glypican-3 levels were significantly lower in OA patients than in healthy controls (P = 0.03), whereas synovial fluid glypican-3 levels were remarkably greater than in paired plasma samples of OA patients (P < 0.001). Subsequent analysis demonstrated that plasma and synovial fluid glypican-3 levels were inversely associated with the radiographic severity of knee OA (r = -0.691, P < 0.001; r = -0.646, P < 0.001, respectively). Furthermore, there was a positive relationship between plasma and synovial fluid glypican-3 levels in knee OA patients (r = 0.515, P < 0.001). Additionally, overexpression of glypican-3 mRNA was observed in inflamed synovium of OA patients (P = 0.021).

Conclusions: The present study revealed that plasma and synovial glypican-3 levels were negatively associated with radiographic severity of knee OA. Glypican-3 could emerge as a potential biomarker for reflecting the severity of knee OA and might play a plausible role in the pathophysiology of degenerative joint disease.

Keywords: glypican-3; knee; osteoarthritis; plasma; synovial fluid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Glypicans
  • Humans
  • Osteoarthritis, Knee* / diagnostic imaging
  • RNA, Messenger
  • Radiography
  • Severity of Illness Index
  • Synovial Fluid*


  • Glypicans
  • RNA, Messenger