Increased Synovial CD14 mRNA Expression and Proportion of CD14high Subsets in Early-Stage Hip Osteoarthritis: Propensity Matched Score Analysis

Abstract

The pathophysiology of early-stage hip osteoarthritis (EOA) is not fully understood. Although a previous study in an age-unmatched cohort reported that the number of macrophages was increased in knee EOA compared to late OA (LOA), it remained unclear whether increased macrophages in EOA accurately reflect EOA pathology. We investigated the differences in CD14 expression levels between EOA and LOA using age-unmatched and -matched cohorts. Synovial tissues were obtained from 34 EOA (Tönnis grades 0 and 1) and 80 LOA (Tönnis grades 2 and 3) patients. To correct for differences in demographics between patients with LOA and EOA, we also created propensity score-matched cohorts (16 EOA and 16 LOA). CD14 expression and its association with pain was estimated in LOA and EOA before and after propensity matching. We performed flow cytometry on tissues from the 16 patients, with 8 from each group, to assess for CD14+ subsets in the cells. The CD14 expression in EOA was higher than that in LOA both before and after propensity matching. The proportion of CD14^high subsets in EOA was higher than that in LOA. The CD14 expression was associated with pain in EOA before matching. However, no difference was observed between the pain and CD14 expression after matching in EOA. The increased CD14 expression and the proportion of CD14^high subsets may be important features associated with hip EOA pathology. To accurately compare early and late OA, the analysis of a propensity score-matched cohort is necessary.

Keywords: CD14+ cells; CD14high subsets; early-stage osteoarthritis; hip osteoarthritis; hip pain.

Figure 1

Comparison of synovial CD14 expression in patients with early and late hip osteoarthritis (EOA and LOA, respectively). Synovial CD14 expression in the before (A) and after (B) propensity matching cohorts. X axis: white and gray boxes represent the patients with EOA and LOA, respectively. Y axis: relative CD14 mRNA expression. The Mann–Whitney U-test was used for analysis. p < 0.05 indicates statistical significance. Boxes represent median and IQR (interquartile range, 25–75th percentiles); small circle represent values outside 1.5 × IQR.

Figure 2

Comparisons of synovial CD14 expression between moderate and severe pain in patients with early hip osteoarthritis (EOA) and late hip osteoarthritis (LOA). Synovial CD14 expression (y axis) in EOA patients with moderate (gray boxes) and severe (black boxes) pain before (A) and after (B) propensity matching. Synovial CD14 expression in LOA patients with moderate and severe pain before (C) and after (D) propensity matching. Boxes represent median and IQR (interquartile range, 25–75th percentiles); whiskers represent range within 1.5 × IQR; and small circle represent values outside 1.5 × IQR. Y axis, relative CD14 mRNA expression. The Mann–Whitney U-test was used for analysis. p < 0.05 indicates statistical significance.

Figure 3

Differences in the proportion of CD14+ cell subsets in synovium from patients with early hip osteoarthritis (EOA) and late hip osteoarthritis (LOA) using flow cytometric analysis. Dot−plot analysis of CD14+ cells among synovial cells after CD45 gating in patients with EOA (A) and LOA (B). X axis, CD14; Y axis, CD45. S₁ and S₂ represent the CD14^low and CD14^high cell subsets, respectively. (C) The comparison of percentage of CD14^high subsets in CD45+ cells between EOA (white) and LOA (gray). (D) The comparison of percentages of CD14^low subsets in CD45+ cells between EOA (white) and LOA (gray). 3C represents the percentage of CD14^high, and 3D represents the percentage of CD14^low cells of patients with EOA (white) and LOA (gray). Boxes represent median and IQR (interquartile range, 25−75th percentiles); small circle represent values outside 1.5 × IQR. Mann–Whitney U-test was used for analysis. p < 0.05 indicates statistical significance.