Normal Human Synovial Fluid Exhibits Stable Hyaluronic Acid and Proteoglycan 4 Levels Across Age and Sex

Abstract

Objective

Hyaluronic acid (HA) and proteoglycan 4 (PRG4) are the primary lubricants in synovial fluid (SF), critical to its function and overall joint health. SF composition and lubricating ability has been primarily investigated in the context of disease; however, baseline ranges in normal SF remain unclear. This study aimed to quantify PRG4 and HA concentrations and evaluate lubrication performance in human SF without any joint pathology.

Methods

SF was obtained from 33 cadaveric donors, with samples collected bilaterally in seven donors. Mean donor age was 60 ±14 years and 51.5% were female. Concentrations of HA and PRG4 were quantified and SF lubrication under static and dynamic fiction conditions was assessed. Sex differences, age correlations, and intra-individual variability in biochemical and frictional properties were analyzed.

Results

HA ranged from 0.44 to 10.13 mg/mL (mean: 2.66 ±2.05 mg/mL), while PRG4 levels ranged from 183.51 to 303.25 μg/mL (mean: 251.15 ±32.16 μg/mL). Neither lubricant correlated with age (HA: rs=0.03, p=0.88; PRG4: r=0.12, p=0.52) or sex (both p>0.5), nor showed intra-individual differences (both p>0.40). Mean static friction (0.63 ±0.08) exceeded dynamic friction (0.48 ±0.04), and both were independent of age, sex, and HA and PRG4 levels (all p>0.2).

Conclusion

Baseline concentrations of HA and PRG4 and SF lubrication properties in normal SF were independent of age and sex, with no significant association between lubricant composition and function. These findings provide a reference for normal SF lubricant composition and lubrication function and will aid in the understanding of SF lubrication dysregulation in disease states.