Table 1.
Molecular changes in humans with osteoarthritis.
| Authors (year) | Subjects' characteristics | Sample | Molecules and cells involved | |||||
|---|---|---|---|---|---|---|---|---|
| Cytokines | Chemokines | Matrix metalloproteinases (MMPs) | Immune cells | Other proteins | miRNA | |||
| Hou et al. (2017) [9] | OA patients, n = 10 Non-OA patients, n = 8 |
Synovial tissue | ↑ CX3CL1 | ↑ MMP-3 | ||||
| Deligne et al. (2015) [14] | OA patients, n = 32, mean age 70.3 ± 9.8 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, n = 40, median age 65 years Healthy control, n = 13, 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, n = 16 Healthy control, n = 16 |
Blood Synovial fluid |
↑ IL-10 and TGF-β | ↑ LAG-3+ Treg cells | ||||
| Min et al. (2017) [20] | Knee OA patients, n = 148, mean age 68.0 years Healthy control, n = 101, mean age 57.7 years |
Fasting blood | ↑ TNF-α | ↑ Serum OPG ↓ DKK1 |
||||
| Chang et al. (2015) [21] | OA patients, n = 15, mean age 60.7 ± 4.4 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, n = 58, median age 66 years Healthy control, n = 30, 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, n = 6, mean age 31.2 ± 2.91 years | Articular cartilages | ↑ IL-1α, IL-1β, and TNF-α | ↑ MMP-13 | ↑ p65 nuclear level ↓ IκBα degradation |
|||
| Ding et al. (2015) [24] | OA patients, n = 25, mean age 66.6 years | Synovial tissues | ↑ MMP-2 | ↑ Cadherin-11 | ||||
| Xu et al. (2015) [26] | OA patients, n = 5 Normal control, n = 3 |
Articular cartilage | ↑ Sam68 expression | |||||
| Jiang et al. (2017) [28] | OA patients, n = 20 | 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, n = 10 Normal control, n = 10 |
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, n = 20 Normal control, n = 20 |
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, n = 152, mean age 73 ± 9 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, n = 4, mean age 53.6 ± 26.6 years Control: DDWR patients, n = 2, mean age 24.5 ± 2.1 years |
Synovial fluid | ↑ IL-17, IL-1β, IL-22, and RANKL | ↑ CCL5, CCL20, CCR5, and CCR7 | ||||
| Alaaeddine et al. (2015) [46] | OA patients, n = 21, mean age 67 ± 19 years Non-OA donor, n = 8, mean age 30 ± 27 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, n = 5, median age 34 years End-stage OA patients, n = 5, 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, n = 11, average age 49 years Healthy control, n = 12, average age 42 years |
Knee articular cartilage Blood |
↑ IL-6, IL-8 | ↑ P2X7R | ↓ miR-373 | |||
| Böhm et al. (2016) [50] | OA patients, n = 22, mean age 66.7 years | Synovial tissue | ↑ IL-6 and IL-8 | |||||
| Wu et al. (2018) [51] | OA patients, n = 40, mean age 43 years Normal control, n = 10, 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, n = 8 | Articular cartilage | ↑ IL37, IL-6, and IL-8 | ↑ MMP-1, MMP-3, and MMP-13 | ↑ ADAMTS5 | |||
| Ding et al. (2017) [54] | OA patients, n = 72, mean age 63.89 ± 14.34 years, and disease duration 4.56 ± 3.9 years Healthy control, n = 40, mean age 62.32 ± 14.15 years |
Blood Synovial fluid Synovial tissues |
↑ IL-37, IL-1β, TNF-α, and IL-6 | |||||
| Mabey et al. (2016) [55] | OA patients, n = 32, mean age 64.6 ± 6.2 years Healthy control, n = 14, mean age 63.9 ± 6.4 years |
Blood samples Synovial fluid |
↑ IL-2, IL-4, IL-6, and IL-10 | |||||
| He et al. (2017) [56] | OA patients, n = 12, mean age 65.8 ± 3.5 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, n = 35 Normal control, n = 37 |
Synovial tissue Synovial fluid |
↑ CCL2 | |||||
| Chen et al. (2018) [64] | Facet joint OA patients, n = 48, mean age 64 ± 1.7 years Healthy control, n = 10, mean age 25 ± 1.2 years |
Facet joint tissues | ↑ CCL4 and CCL4L2 | ↑ DKK2 | ||||
| Belluzzi et al. (2018) [67] | OA patients, n = 5, 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, n = 7 Healthy control, n = 9 |
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, n = 12 Patients with other joint diseases, n = 12 |
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, n = 13, mean age 77.5 ± 10 years | Articular cartilages | ↑ IL-6 | ↑ MMP-13 | ↑ COX2, PGE-2, and nitrite | |||
| Peng et al. (2017) [76] | OA patients, n = 5, mean age 65.2 ± 3.2 years Normal control, n = 3, mean age 31.0 ± 5.9 years |
Synovial tissues | ↑ MMP-13 | ↓ DUSP1 ↑ p-p38, p-JNK, and COX-2 |
||||
| Ma et al. (2018) [77] | OA patients, n = 30 | 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, n = 31, average age 76.4 years Normal control, n = 12, 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, n = 8 Normal control, n = 12 |
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, n = 20 for cartilage samples, mean age 66.6 ± 9.9 years; n = 25 for synovial fluid samples, mean age 63.6 ± 15.7 years | Knee articular cartilage Synovial fluid |
↑ IL-6 | ↑ MMP-3 | ↑ TSG-6, TIMP1, and VEGF | |||
| Chen et al. (2018) [84] | OA patients, n = 20, mean age 62 ± 9.2 years Healthy donor, n = 20, mean age 55.2 ± 8.64 years |
Articular cartilage | ↑ IL-6 | ↑ MMP-3 | ↑ TAK1, nitrite, PGE2, and p-p65 ↓ IkBα |
↓ miR-149 | ||
| Alunno et al. (2017) [86] | OA patients, n = 24 | Synovial fluid FLS |
↑ MMP-2 | |||||
| Gui et al. (2017) [88] | OA patients, n = 10, mean age 63.4 years | Articular cartilages | ↑ SOCS3, NF-κB, and COX2 | |||||
| Terauchi et al. (2016) [95] | OA patients, n = 5 | Articular cartilage | ↑ Runx2 | |||||
| Tao et al. (2015) [96] | OA patients, n = 10, mean age 50 ± 10 years Healthy control, n = 10, mean age 55 ± 10 years |
Articular cartilage | ↑ KPNA2 | |||||
| Struglics et al. (2016) [100] | OA patients, n = 24, 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, n = 159, mean age 63.7 ± 11.8 years | Synovial fluid Blood |
↑ CD163 and CD14 | |||||
| Mao et al. (2017) [107] | OA patients, n = 8, mean age 65.8 ± 2.24 years Healthy donor, n = 8, mean age 64.4 ± 2.86 years Normal donors for bone marrow, n = 6, mean age 37 years |
Bone marrow Cartilage tissues |
↑ ADAMTS-4 and ADAMTS-5 ↓ ACAN |
↓ miR-92a-3p | ||||