Diminished cartilage-lubricating ability of human osteoarthritic synovial fluid deficient in proteoglycan 4: Restoration through proteoglycan 4 supplementation
Article first published online: 28 NOV 2012
Copyright © 2012 by the American College of Rheumatology
Arthritis & Rheumatism
Volume 64, Issue 12, pages 3963–3971, December 2012
How to Cite
Ludwig, T. E., McAllister, J. R., Lun, V., Wiley, J. P. and Schmidt, T. A. (2012), Diminished cartilage-lubricating ability of human osteoarthritic synovial fluid deficient in proteoglycan 4: Restoration through proteoglycan 4 supplementation. Arthritis & Rheumatism, 64: 3963–3971. doi: 10.1002/art.34674
- Issue published online: 28 NOV 2012
- Article first published online: 28 NOV 2012
- Accepted manuscript online: 29 AUG 2012 03:08PM EST
- Manuscript Accepted: 9 AUG 2012
- Manuscript Received: 23 MAR 2012
- National Science and Engineering Research Council of Canada
- Canadian Arthritis Network
- Alberta Innovates Technology Futures
- Alberta Innovates Health Solutions (OA Team Grant)
- University of Calgary (funding from the Faculty of Kinesiology and from the Center for Bioengineering Research and Education, Schulich School of Engineering)
The purposes of this study were 1) to quantify the proteoglycan 4 (PRG4) and hyaluronan (HA) content in synovial fluid (SF) from normal donors and from patients with chronic osteoarthritis (OA) and 2) to assess the cartilage boundary–lubricating ability of PRG4-deficient OA SF as compared to that of normal SF, with and without supplementation with PRG4 and/or HA.
OA SF was aspirated from the knee joints of patients with symptomatic chronic knee OA prior to therapeutic injection. PRG4 concentrations were measured using a custom sandwich enzyme-linked immunosorbent assay (ELISA), and HA concentrations were measured using a commercially available ELISA. The molecular weight distribution of HA was measured by agarose gel electrophoresis. The cartilage boundary–lubricating ability of PRG4-deficient OA SF, PRG4-deficient OA SF supplemented with PRG4 and/or HA, and normal SF was assessed using a cartilage-on-cartilage friction test. Two friction coefficients (μ) were calculated: static (μstatic, Neq) and kinetic (<μkinetic, Neq>) (where Neq represents equilibrium axial load and angle brackets indicate that the value is an average).
The mean ± SEM PRG4 concentration in normal SF was 287.1 ± 31.8 μg/ml. OA SF samples deficient in PRG4 (146.5 ± 28.2 μg/ml) as compared to normal were identified and selected for lubrication testing. The HA concentration in PRG4-deficient OA SF (mean ± SEM 0.73 ± 0.08 mg/ml) was not significantly different from that in normal SF (0.54 ± 0.09 mg/ml). In PRG4-deficient OA SF, the molecular weight distribution of HA was shifted toward the lower range. The cartilage boundary–lubricating ability of PRG4-deficient OA SF was significantly diminished as compared to normal (mean ± SEM <μkinetic, Neq> = 0.043 ± 0.008 versus 0.025 ± 0.002; P < 0.05) and was restored when supplemented with PRG4 (<μkinetic, Neq> = 0.023 ± 0.003; P < 0.05).
These results indicate that some OA SF may have decreased PRG4 levels and diminished cartilage boundary–lubricating ability as compared to normal SF and that PRG4 supplementation can restore normal cartilage boundary lubrication function to these OA SF.