Hyaluronan molecular weight distribution is associated with the risk of knee osteoarthritis progression

Abstract

Objective: We investigated the relationship between the molecular weight (MW) distribution of hyaluronan (HA) in synovial fluid (SF) and risk of knee osteoarthritis (OA) progression.

Methods: HA MW was analyzed for 65 baseline knee SFs. At 3-year follow-up, knees were scored for change in joint space narrowing (JSN), osteophyte (OST) progression, or occurrence of total knee arthroplasty (TKA). HA MW distribution was analyzed using agarose gel electrophoresis (AGE), and its relationship to OA progression was evaluated using logistic regression. The association between HA MW and self-reported baseline knee pain was analyzed using Pearson's correlation coefficients.

Results: Knee OA was categorized as non-progressing (OST-/JSN-, 26 knees, 40%), or progressing based on OST (OST+/JSN-, 24 knees, 37%), OST and JSN (OST+/JSN+, 7 knees, 11%) or total knee arthroplasty (TKA, 8 knees, 12%). The MW distribution of HA in baseline SFs was significantly associated with the odds of OA progression, particularly for index knees. After adjusting for age, gender, BMI, baseline X-ray grade and pain, each increase of one percentage point in %HA below 1 million significantly increased the odds of JSN (odds ratios (OR) = 1.45, 95% CI 1.02-2.07), TKA or JSN (OR = 1.24, 95%CI 1.01-1.53) and the odds of any progression (OR = 1.16, 95% CI 1.01-1.32). HA MW distribution significantly correlated with pain.

Conclusion: These data suggest that the odds of knee OA progression increases as HA MW distribution shifts lower and highlight the value of reporting MW distribution rather than just average MW values for HA.

Keywords: Hyaluronan; Molecular weight; Osteoarthritis progression; Synovial fluid.

Fig. 1

Illustration of a representative result of hyaluronan (HA) electrophoresed on an agarose gel to analyze the MW distribution of HA. Patients #38 and #39 were chosen as examples because both had SF available for both the RK and LK. Patient #38 had K-L grade 2 for both knees at baseline and TKA outcome for both knees. Patient #39 had K-L grade 3 in both knees at baseline and OST+/JSN− outcome for both knees. Patient samples are in lanes 1 (#39 LK), 3 (#39, RK), 4 (#38, LK) and 6 (#38, RK). Lanes 7, 9 and 10 represent three sets of HA standards to cover a broad MW range: lane 7 Mega ladder (ML) standards are 1.5, 3.1, 4.4 and 6.1 million MW; lane 9 High ladder (HL) standards are 0.51, 0.67, 0.94, 1.14 and 1.5 million MW; and lane 10 Super-mega ladder (SL) standards are 2, 4, 6 and 8 million MW.

Fig. 2

Laser scan of selected lanes from the agarose gel in Fig. 1 for SF from patient # 38, LK, TKA outcome (top panel); and patient # 39, LK OST+/JSN− outcome (bottom panel). The area under the curve to the left of the vertical 1 million MW line represents the weight %, preponderance of lower MW species in a sample.. In these examples, patient #38 has a weight % below 1 million of 26% for the LK sample, while patient #39 has a weight % below 1 million of 14% for LK sample.