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. Author manuscript; available in PMC: 2022 May 1.
Published in final edited form as: Nat Rev Rheumatol. 2022 Feb 14;18(5):258–275. doi: 10.1038/s41584-022-00749-9

Table 1 ∣.

Clinical relevance of cell types associated with synovitis in OA

Cell type Markers Clinical relevance Refs
Macrophages Folate receptor detected by 99mTc-EC20 SPECT–CT The quantity of activated macrophages correlated with radiographic OA severity and pain and stiffness 71
CD14+CD16+ macrophages in synovial fluid express mature macrophage marker 25F9 (indicating activation) CD14+ macrophages/total macrophages ratio in synovial fluid is a predictor of KOOS and WOMAC scores, regardless of CD16 expression 63
CD14 and CD163 in synovial fluid significantly associated with activated macrophages (detected by 99mTc-EC20 SPECT–CT), in the capsule (P = 0.002 and P = 0.005, respectively) and in the synovium (P = 0.0005 and P = 0.002, respectively) CD14 and CD163 presence in the synovial fluid is associated with osteophyte severity
Synovial fluid CD14 and serum CD163 associated with severity of joint space narrowing
Severity of self-reported knee joint symptoms associated with both synovial fluid (β = 0.773; P = 0.003) and serum (β = 0.641; P = 0.031) CD14 levels
71
CD11c+/CD206+ or CD86+/CD163+ ratio in synovial fluid Associated with KL grading and severity of knee OA in patients 72
Mannose receptors MRC1 and MRC2 MRC1 and MRC2 recognize collagen, promoting its internalization and lysosomal degradation
Resulting improvement in collagen turnover restores ECM homeostasis in the joint and ameliorates cartilage destruction
Type II collagen helps to maintain expression of anti-inflammatory macrophage-related genes and pro-chondrogenic cytokines
77
SEPP1, FLOR2, STAB1, TXNIP and CD169 Gene expression profile is indicative of enhanced phagocytic activity and immunosuppressive activity, suggesting an immunoregulatory role 58
CCR2+ macrophages Present in human synovium
Invasive cells that are associated with cartilage erosion in OA
65
CCL3, CCL4, IL1B and TNF Pro-inflammatory macrophages 58
FLS CD34THY1+ FLS Less abundant in OA synovium than in RA synovium (8% versus 22% of cells, respectively)
Perivascular location, proliferative and secrete pro-inflammatory cytokines
Proportion of these FLS is correlated with synovitis and synovial hypertrophy assessed by ultrasonography
90
CD34THY FLS Located in synovial lining
Express the osteoblastic bone formation promoter BMP6 (involved in osteophyte formation)
More abundant in OA than in RA synovium
90
CADM1, COL8A2 and DKK3 Located in synovial lining
DKK3 is a strong inhibitor of cytokine-induced collagen loss
59,259
PTGDS, CXCL3, RSPO3, NRN1, NFKBIA, CXCL2, GEM, VCAM1, LIF, IL6 and INHBA Associated with painful synovial sites in early OA 52
HSPA1A, DNAJB1, SLC39A8, HTRA3, ATF3, PTGIS and BNIP3 Associated with painful synovial sites in end-stage OA 52

ECM, extracellular matrix; FLS, fibroblast-like synoviocytes; KL, Kellgren and Lawrence; KOOS, Knee Injury and Osteoarthritis Outcome Score; OA, osteoarthritis; RA, rheumatoid arthritis; TNF, tumour necrosis factor.