Correlation between CD163 expression and resting pain in patients with hip osteoarthritis: Possible contribution of CD163+ monocytes/macrophages to pain pathogenesis

Abstract

Expression of CD163, a scavenger receptor specifically expressed by monocytes and macrophages, is elevated in the synovial tissue of patients with knee osteoarthritis (OA) compared with healthy controls. However, the association between CD163 expression in the synovium and pain in OA patients is unclear. We investigated the correlation between synovial CD163 expression and resting and active pain levels in patients with hip osteoarthritis (HOA). To investigate the possible contribution of CD163+ subsets to pain pathogenesis, we compared pain‐related cytokine expression and M1/M2 macrophage marker expression in CD163+ and CD163− cells. We performed flow cytometric analysis to study the CD163+ cell population. We also examined pain‐related cytokine expression and M1/M2 macrophage marker expression on CD163+ CD14high and CD163+ CD14low cells using cell sorting. Synovial CD163 expression significantly correlated with resting pain levels (p = 0.006; R = 0.321), but not active pain levels (p = 0.155; R = 0.169). Expression of the M1 macrophage marker CD80 was significantly higher in CD163+ than CD163− cells (p = 0.010), as was the expression of M2 macrophage markers CD206 and IL10 (CD206, p = 0.014; IL10, p = 0.005), and TNFA and IL1B (TNFA, p = 0.002; IL1B, p = 0.001). TNFA expression was significantly higher in CD163+ CD14low than CD163+ CD14high cells, while IL1B, IL10, and CD206 expression were comparable among these subsets. Our findings suggest that CD163 expression is associated with higher resting pain scores. As TNF‐α plays a role in the pain process, CD163+ CD14low cells expressing TNFA may be a potent contributor to the pathogenesis of resting pain in HOA.

Bibliometric and visualization analysis of macrophages associated with osteoarthritis from 1991 to 2021

“…reported that elevated CGRP by CD14-positive macrophages may contribute to increased OA pain ( 48 ). In addition, researchers reported that CD163+CD14 low macrophages expressing TNF-α might be a vital contributor to the OA pain ( 50 ). These molecular factors contribute to the pain of OA and as a potential therapeutic target in OA pain treatment and should be further explored in the future.…”

“…In addition, the mechanism research of macrophages has also drawn many researchers' attention. For example, NO was found to induce apoptosis and proinflammatory cytokines secretion, while others reported that it could protect chondrocytes and attenuates macrophagemediated inflammation (49)(50)(51)(52)(53). Therefore, exploring the mechanisms underlying on the macrophage and OA progression.…”

Six macrophage-associated genes in synovium constitute a novel diagnostic signature for osteoarthritis

“…Activated macrophages can polarize into M1- and M2-like macrophages, playing proinflammatory and anti-inflammatory roles in OA, respectively ( 11 ). Under pathological conditions, the balance of proinflammatory and anti-inflammatory driven by M1/M2 macrophages is broken, resulting in immunogenic damage to osteoarticular tissues and contributing to the resting pain symptom ( 12 ). In addition, accumulation of synovial macrophages also contributes to osteoarthritis joint pain through various mechanisms, such as pain sensitization ( 13 ), high expression of the neurotrophin nerve growth factor ( 14 ), and neuroimmune cross talk ( 15 ).…”

Expanded CD1c+CD163+ DC3 Population in Synovial Tissues Is Associated with Disease Progression of Osteoarthritis

“…CD163 expression in the synovium is elevated in patients with OA compared to healthy controls [ 9 ]. The soluble form of CD163, sCD163, is cleaved from CD163 during inflammation by ADAM-17, and elevated sCD163 levels in blood reflect inflammation and radiographic severity in OA [ 10 ]. CD163 expression is associated with higher resting pain scores [ 10 ].…”

“…The soluble form of CD163, sCD163, is cleaved from CD163 during inflammation by ADAM-17, and elevated sCD163 levels in blood reflect inflammation and radiographic severity in OA [ 10 ]. CD163 expression is associated with higher resting pain scores [ 10 ]. In the current study, significantly increased levels of inflammatory DC3s were observed in the synovium compared with PBMCs and synovial fluid (SF).…”