Table 1: Role of the essential cells implicated in OA pathogenesis.

Cell typeRoleComments

Macrophages(i) Line intimal layer [5, 14] 
(ii) Required for production of MMPs and cartilage damage [5, 14] 
(iii) TNFα, IL-1, MMP, TGFβ, IL-10, IL-12, and chemokine production [29] 
(iv) Mediators of TGFβ induced osteophyte formation [76] 
(v) Possess TLRs [14]

T cell (TCR = T-cell receptor)(i) Line subintimal layer [5]  
(ii) Present in different stages of activation: early (CD69+), intermediate (CD25,38+), and late (CD45RO+) [34]
(iii) Increased CD4+/CD8+ ratio in OA knees versus control [35]  
(iv) Th1 > Th2 subset, as well as increased Th1 cytokine product IFNγ [34, 36]  
(v) Increased CD3ε+ T cells and CD3ε+/CD3ζ+ T cell ratio in OA synovium and decreased ratio of CD3ζ+ T cells [65] 
(vi) Produce chemokines attractant to macrophages [65]  
(vii) CDR3 similarity in TCR [77]  
(viii) Several autoantigens including those on chondrocyte membrane have been identified [31, 78, 79] 
(ix) Cartilage linking protein and G1 domain of aggrecan have shown promise as potential autoantigens to follow [31, 78, 79]
(i) Suggestive of chronic inflammation 
(ii) Suggestive of oligoclonal expansion and antigen-driven response

Mast cell (MC)(i) Numbers are at least as high as those in RA synovium [5]  
(ii) Mostly in subintimal layer and around blood vessels [22]  
(iii) Levels positively correlated with total cellular infiltrate, however no correlation with ESR [22]  
(iv) Degranulated MCs found most commonly in intimal layer [23]  
(v) Higher ratio of tryptase to tryptase/chymase phenotype in OA than controls [24]  
(vi) Selective expansion of tryptase MC phenotype [24]
(i) MCs lie around blood vessels and mediate vascular permeability hinting at crucial role of MCs, however not related to ESR and degranulated phenotype seen in intimal layer 
(ii) Tryptase phenotype suggestive of degranulation

B cells(i) Not always present or may be present in small numbers [24]  
(ii) Mostly in subintimal layer [5]  
(iii) Undergo oligoclonal expansion with similar CDR3 regions [80, 81] 
(iv) Evidence of somatic hypermutation [80, 81]  
(v) In patients with moderate to strong infiltration, there were presence of germinal centers and increased T-cell populations [80, 81]  
(vi) Potential role as antigen presenting cell [80, 81]  
(vii) Several autoantigens have been identified including those on the chondrocyte membrane but multiple antigens have been discovered and patterns have yet to be characterized [31]  
(viii) Elevated antibody titer to cartilage membrane in OA patients versus control [82] 
(ix) Secrete IL-6 [83]
(i) Suggestive of antigen-driven response

Fibroblast(i) Activated by both IL-1β and TNFα and must neutralize both to decrease activation [29] 
(ii) Produces MMPs, IL-6, IL-8, ADAMTS-4,5, and MCP-1 [29]

NK cell(i) May have role in early pathogenesis of OA: found to have CD16+CD56+ phenotype [19] positive for granzymes A and B [19, 21] and CD16CD56+ phenotype negative for granzymes A and B [20]  
(ii) Poor in vitro IFNγ production upon stimulation in late OA patients [20]  
(iii) Stimulated by IL-15 [66]
(i) Suggestive of activation/exhaustion phenotypes

Neutrophil (PMN)(i) Generally not found in OA synovial tissue, but sometimes present [5] 
(ii) HNP1-3 (mainly produced by PMNs) found in synovia of OA patients, with levels inhibited by TNFα stimulation [27] 
(iii) NGAL (mainly produced by PMNs) found in OA synovia complexed with MMP-9, decreasing its degradation and increasing glycosaminoglycan levels released from cartilage explants [27]
(i) PMNs may play a role in the earliest stages of OA and therefore might not be expected to be identified in most studies of established OA samples