Mediators of Inflammation

Review Article

The Role of Inflammation in the Pathogenesis of Osteoarthritis

Table 1

Molecular changes in humans with osteoarthritis.


Authors (year)	Subjects’ characteristics	Sample	Molecules and cells involved
Authors (year)	Subjects’ characteristics	Sample	Cytokines	Chemokines	Matrix metalloproteinases (MMPs)	Immune cells	Other proteins	miRNA

Hou et al. (2017) [9]	OA patients, Non-OA patients,	Synovial tissue		↑ CX3CL1	↑ MMP-3
Deligne et al. (2015) [14]	OA patients, , mean age years	Synovial tissues	↑ IL-1β, IL-6, IL-8, IL-18, IL17, IL-22, and TGFβ1		↑ MMP-2	↑ Leukocyte (macrophages, T-lymphocytes, B-lymphocytes, neutrophils) infiltrates	↑ MPO
Shan et al. (2017) [15]	OA patients, , median age 65 years Healthy control, , median age 61 years	Fasting venous blood	↑ IL-21, IFN-γ, and IL-17A			↑ PD-1+CXCR5+CD4+ T cells, ICOS+CXCR5+CD4+ T cells, and IL-21+CXCR5+CD4+ T cells	↑ CRP
Xia et al. (2017) [16]	OA patients, Healthy control,	Blood Synovial fluid	↑ IL-10 and TGF-β			↑ LAG-3+ Treg cells
Min et al. (2017) [20]	Knee OA patients, , mean age 68.0 years Healthy control, , mean age 57.7 years	Fasting blood	↑ TNF-α				↑ Serum OPG ↓ DKK1
Chang et al. (2015) [21]	OA patients, , mean age years	Peripheral blood Articular synovial membrane	↑ TNF-α and IL-1β	↑ CCR3 and eotaxin-1(CCL11)	↑ MMP-9
Ni et al. (2015) [22]	OA patients, , median age 66 years Healthy control, , median age 60 years	Blood Synovial fluid Synovial tissues	↑ TNF-α, IL-1β, and IL-6				↑ FSTL1, p-p65, and p-IκBα ↓ p53 and p21
Ma et al. (2015) [23]	OA patients, , mean age years	Articular cartilages	↑ IL-1α, IL-1, and TNF-		↑ MMP-13		↑ p65 nuclear level ↓ IκBα degradation
Ding et al. (2015) [24]	OA patients, , mean age 66.6 years	Synovial tissues			↑ MMP-2		↑ Cadherin-11
Xu et al. (2015) [26]	OA patients, Normal control,	Articular cartilage					↑ Sam68 expression
Jiang et al. (2017) [28]	OA patients,	Articular cartilages					↑ BRD4
Qu et al. (2018) [30]		Articular cartilage	↑ IL-6 and TNF-α		↑ MMP-13		↓ Ghrelin, ACAN, col2, sox-9, and GAG ↑ ADAMTS-5 and iNOS
Xia et al. (2016) [31]	OA patients, Normal control,	Blood Articular cartilage Synovial tissues	↑ TNFα, IL-6, and IL8				↑ COX-2, iNOS, and p-p65 ↓ IkBα	↑ miR-381a-3p
Zhang et al. (2016) [35]	OA patients, Normal control,	Articular cartilages	↑ IL-6, TNF-α		↑ MMP-13		↓ ACAN, col2, and Ik-Bα expression ↑ TRAF2 and p-p65 expression	↓ miR-502-5p
Snelling et al. (2017) [41]	OA patients, , mean age years	Blood Synovial fluid	14 patients had detectable IL-17 in SF with ↑ IL-6	↑ CCL7 in the 14 patients			↑ Leptin, resistin, and NGF
Monasterio et al. (2018) [42]	TMJ-OA patients, , mean age years Control: DDWR patients, , mean age years	Synovial fluid	↑ IL-17, IL-1β, IL-22, and RANKL	↑ CCL5, CCL20, CCR5, and CCR7
Alaaeddine et al. (2015) [46]	OA patients, , mean age years Non-OA donor, , mean age years	Knee cartilage	↑ IL-6 by CCL20	↑ CCL20 and CCR6	↑ MMP-1 and MMP-13 by CCL20		↑ PGE2 and proteoglycan by CCL20 ↑ ADAMTS-5 and col10 mRNA expression
Favero et al. (2018) [47]	Early-stage OA patients, , median age 34 years End-stage OA patients, , median age 62 years	Synovial tissues	↑ IL-6 and IL-8	↑ CCL2, CCL21, and CCL5 (RANTES)	↑ MMP-3 and MMP-10		↑ TIMP-2, TIMP-4 ↑ GAG and ACAN CS846 epitope
Capsoni et al. (2015) [48]		Articular cartilage	↑ IL-6 and IL-8		↑ MMP-3 and MMP-13		↑ NO, iNOS, TIMP-3, and TIMP-4
Zhang et al. (2017) [49]	OA patients, , average age 49 years Healthy control, , average age 42 years	Knee articular cartilage Blood	↑ IL-6, IL-8				↑ P2X7R	↓ miR-373
Böhm et al. (2016) [50]	OA patients, , mean age 66.7 years	Synovial tissue	↑ IL-6 and IL-8
Wu et al. (2018) [51]	OA patients, , mean age 43 years Normal control, , mean age 39 years	Synovial tissue	↑ IL-6, IL-8		↑ MMP-3, MMP-13		↓ STC1	↑ miR-454
van Geffen et al. (2016) [53]	OA patients,	Articular cartilage	↑ IL37, IL-6, and IL-8		↑ MMP-1, MMP-3, and MMP-13		↑ ADAMTS5
Ding et al. (2017) [54]	OA patients, , mean age years, and disease duration years Healthy control, , mean age years	Blood Synovial fluid Synovial tissues	↑ IL-37, IL-1β, TNF-α, and IL-6
Mabey et al. (2016) [55]	OA patients, , mean age years Healthy control, , mean age years	Blood samples Synovial fluid	↑ IL-2, IL-4, IL-6, and IL-10
He et al. (2017) [56]	OA patients, , mean age years	Articular cartilage	↑ IL-6, TNF-α, and IFN-γ ↓ IL-4				↑ SOCS1, caspase 9, Bax, Bcl-2, and iNOS
Sun et al. (2015) [59]		Articular cartilage	↑ IL-1R and TNF-α		↑ MMP-1 and MMP-13		↑ PARP-1, iNOS, and p-p65 ↓ TIMP-1
Raghu et al. (2017) [63]	OA patients, Normal control,	Synovial tissue Synovial fluid		↑ CCL2
Chen et al. (2018) [64]	Facet joint OA patients, , mean age years Healthy control, , mean age years	Facet joint tissues		↑ CCL4 and CCL4L2			↑ DKK2
Belluzzi et al. (2018) [67]	OA patients, , median age 68 years	Cartilage Synovial membrane tissues Meniscus IFP	↑ IL-6, IL-1β	↑ CXCL8, CCL21	↑ MMP-10
Huang et al. (2016) [68]		Synovial tissues	↑ IL-6, IL-1β, and TNF-α	↑ MCP-1 (CCL2)			↑ NO, PGE2, iNOS, COX-2, VCAM-1, ICAM-1, ET-1, TF, and p-IkB
Arkestål et al. (2018) [69]	OA patients, Healthy control,	Peripheral blood Bone marrow		↑ CCR2 ↓ CXCR3
Chen et al. (2015) [70]		Synovial tissues	↑ IL-6		↑ MMP-13		↑ COX-2, PGE2, VEGF, p-IKK α/β, p-IkBα, and p-p65 expression
Zeng et al. (2019) [73]	OA patients, Patients with other joint diseases,	Articular cartilage	↑ TNF-α and IL-6		↑ MMP-3 and MMP-13		↑ FOXM1, iNOS, COX-2, NO, PGE2, and p-p65
Xia et al. (2017) [74]		Cartilage tissues	↑ IL-6 and TNF-α		↑ MMP-13		↑ PRMT1, ADAMTS-5, NO, PGE2, iNOS, COX-2, SHH, Gli-1, and Patch 1 ↓ ACAN and COL2A1
Burguera et al. (2014) [75]	OA patients, , mean age years	Articular cartilages	↑ IL-6		↑ MMP-13		↑ COX2, PGE-2, and nitrite
Peng et al. (2017) [76]	OA patients, , mean age years Normal control, , mean age years	Synovial tissues			↑ MMP-13		↓ DUSP1 ↑ p-p38, p-JNK, and COX-2
Ma et al. (2018) [77]	OA patients,	Knee cartilage	↑ IL-8		↑ MMP-13		↑ p-PKR, p-PKC, COX-2, ROS, p-ERK, and p65 activity ↓ SOD, catalase, and PPAR-γ
Haneda et al. (2018) [78]	OA patients, , average age 76.4 years Normal control, , average age 85.1 years	Cartilage tissues			↑ MMP-3, MMP-13		↑ AQP1, ADAMTS-4, and ADAMTS-5 ↓ COL2A1 and ACAN expression
Yang et al. (2017) [81]	OA patients, Normal control,	Articular cartilage			↑ MMP-13		↑ IRF-8
Fu et al. (2016) [82]	Normal donors	Articular cartilage			↑ MMP-1, MMP-3, and MMP-9		↑ NO, PGE2, iNOS, COX-2, ADAMTS-4, ADAMTS-5, HMGB1, and TLR4 expression
Chou et al. (2018) [83]	OA patients, for cartilage samples, mean age years; for synovial fluid samples, mean age years	Knee articular cartilage Synovial fluid	↑ IL-6		↑ MMP-3		↑ TSG-6, TIMP1, and VEGF
Chen et al. (2018) [84]	OA patients, , mean age years Healthy donor, , mean age years	Articular cartilage	↑ IL-6		↑ MMP-3		↑ TAK1, nitrite, PGE2, and p-p65 ↓ IkBα	↓ miR-149
Alunno et al. (2017) [86]	OA patients,	Synovial fluid FLS			↑ MMP-2
Gui et al. (2017) [88]	OA patients, , mean age 63.4 years	Articular cartilages					↑ SOCS3, NF-κB, and COX2
Terauchi et al. (2016) [95]	OA patients,	Articular cartilage					↑ Runx2
Tao et al. (2015) [96]	OA patients, , mean age years Healthy control, , mean age years	Articular cartilage					↑ KPNA2
Struglics et al. (2016) [100]	OA patients, , median age 64 years	Synovial fluid	↑ IL-1β, IL-6, IL-8, and TNF-α				↑ C4d, C3bBbP, and sTCC
Daghestani et al. (2015) [101]	OA patients, , mean age years	Synovial fluid Blood					↑ CD163 and CD14
Mao et al. (2017) [107]	OA patients, , mean age years Healthy donor, , mean age years Normal donors for bone marrow, , mean age 37 years	Bone marrow Cartilage tissues					↑ ADAMTS-4 and ADAMTS-5 ↓ ACAN	↓ miR-92a-3p