Table 3.
Cytokines produced by chondrocytes in native tissue and in culture per cell
| Tissue | Unexpanded chondrocytes | Expanded chondrocytes | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|---|---|
| Cytokine (per mg DNA) | Healthy ( n = 9) | Defect ( n = 16) | Osteoarthritis ( n = 27) | P value | Healthy ( n = 8) | Defect ( n = 10) | Osteoarthritis ( n = 12) | P value | Healthy ( n = 15) | Defect ( n = 13) | Osteoarthritis ( n = 13) | P value |
| IL-1α (pg/mg) | 5 ± 12 | 198 ± 630 | 408 ± 1,062 | 0.844 | 439 ± 268 | 993 ± 743 | 460 ± 271 | 0.006 | 1,718 ± 2,689 | 1,978 ± 1,464 | 2,569 ± 2,528 | 0.006 |
| IL-1β (pg/mg) | 0 ± 0 | 14 ± 41 | 0 ± 2 | 0.336 | 14 ± 33 | 816 ± 968 | 125 ± 151 | <0.001* | 283 ± 368 | 369 ± 270 | 459 ± 408 | 0.010 |
| IL-4 (pg/mg) | 0 ± 0 | 0 ± 1 | 0 ± 1 | 0.536 | 18 ± 49 | 18 ± 40 | 40 ± 76 | 0.691 | 148 ± 224 | 200 ± 163 | 263 ± 259 | 0.002 |
| IL-6 (pg/mg) | 4,813 ± 14,438 | 678 ± 1,867 | 1,840 ± 6,389 | 0.928 | 1,715 ± 397 | 1,739 ± 437 | 1,918 ± 77 | 0.037 | 423 ± 414 | 136 ± 268 | 721 ± 319 | <0.001* |
| IL-7 (pg/mg) | 1,288 ± 378 | 1,120 ± 547 | 1,304 ± 619 | 0.457 | 300 ± 401 | 411 ± 343 | 545 ± 555 | 0.008 | ||||
| IL-8 (ng/mg) | 39 ± 94 | 7 ± 23 | 28 ± 102 | 0.192 | 1,070 ± 572 | 786 ± 625 | 784 ± 399 | 0.036 | 28 ± 36 | 36 ± 43 | 113 ± 85 | <0.00* |
| IL-10 (pg/mg) | 0 ± 0 | 252 ± 783 | 969 ± 3,344 | 0.483 | 3,021 ± 2,455 | 16,529 ± 20,669 | 4,925 ± 3,429 | 0.015 | 5,200 ± 6,788 | 6,524 ± 4,806 | 9,471 ± 9,333 | 0.029 |
| IL-13 (ng/mg) | 0 ± 0 | 378 ± 783 | 545 ± 1,531 | 0.296 | 2,027 ± 597 | 3,249 ± 1,155 | 2,936 ± 1,220 | 0.002 | 4,486 ± 6,088 | 5,614 ± 3,730 | 6,787 ± 5,935 | 0.006 |
| TNFα (pg/mg) | 499 ± 1,020 | 2,054 ± 4,520 | 3,567 ± 8,065 | 0.714 | 253 ± 184 | 414 ± 346 | 426 ± 452 | 0.319 | 183 ± 221 | 217 ± 148 | 310 ± 315 | 0.154 |
| IFNγ (pg/mg) | 0 ± 0 | 175 ± 677 | 0 ± 0 | 0.101 | 50 ± 214 | 54 ± 245 | 173 ± 636 | 0.615 | 538 ± 866 | 720 ± 767 | 1,036 ± 1,287 | 0.079 |
| OSM (pg/mg) | 156 ± 279 | 135 ± 239 | 394 ± 776 | 0.963 | 111 ± 164 | 2,736 ± 3,990 | 369 ± 640 | 0.138 | 26 ± 37 | 26 ± 23 | 46 ± 55 | 0.135 |
| LIF (ng/mg) | 0 ± 0 | 1 ± 4 | 5 ± 13 | 0.238 | 76 ± 50 | 194 ± 127 | 97 ± 56 | 0.005 | 38 ± 37 | 23 ± 16 | 48 ± 24 | 0.000* |
| Adiponectin (ng/mg) | 15,700 ± 12,550 | 60,900 ± 74,720 | 20,000 ± 26,960 | 0.238 | 1,582 ± 903 | 3,689 ± 5,136 | 1,777 ± 1,220 | 0.723 | 20 ± 31 | 22 ± 21 | 36 ± 41 | 0.022 |
| Leptin (ng/mg) | 14 ± 29 | 75 ± 151 | 161 ± 199 | 0.009 | 22 ± 7 | 26 ± 7 | 22 ± 9 | 0.125 | 22 ± 24 | 29 ± 18 | 35 ± 27 | 0.014 |
| MCP1 (pg/mg) | 672 ± 1,890 | 806 ± 1,067 | 2,216 ± 3,780 | 0.068 | 376 ± 148 | 626 ± 474 | 331 ± 219 | 0.065 | 43 ± 14 | 38 ± 20 | 53 ± 49 | 0.176 |
| RANTES (pg/mg) | 0 ± 0 | 986 ± 2,687 | 1,074 ± 2,852 | 0.208 | 129 ± 149 | 63 ± 80 | 106 ± 89 | 0.057 | 3 ± 4 | 1 ± 1 | 4 ± 4 | 0.034 |
| bFGF (ng/mg) | 196 ± 527 | 514 ± 762 | 760 ± 923 | 0.089 | 12 ± 15 | 39 ± 68 | 11 ± 18 | 0.427 | 20 ± 17 | 23 ± 14 | 34 ± 26 | 0.021 |
| HGF (pg/mg) | 3,262 ± 6,163 | 5763 ± 10,551 | 3,911 ± 4,661 | 0.565 | 151 ± 243 | 431 ± 470 | 353 ± 534 | 0.118 | 4,243 ± 6,533 | 5,314 ± 4,061 | 7,242 ± 7,595 | 0.004 |
| VEGF (ng/mg) | 33 ± 22 | 173 ± 133 | 66 ± 53 | <0.001* | 638 ± 468 | 828 ± 522 | 742 ± 298 | 0.333 | 126 ± 23 | 133 ± 29 | 124 ± 25 | 0.610 |
| IL-1RA (pg/mg) | 475 ± 960 | 990 ± 1938 | 1,871 ± 7,209 | 0.868 | 2,611 ± 2,167 | 20,259 ± 2,3520 | 11,005 ± 17,284 | 0.002 | 349 ± 260 | 433 ± 260 | 579 ± 442 | 0.031 |
| IL-6Rα (pg/mg) | 8,217 ± 2,190 | 5,397 ± 5,195 | 4,666 ± 5,094 | 0.037 | 3,276 ± 10,387 | 593 ± 324 | 456 ± 333 | 0.064 | ||||
To compare the production of cytokines by chondrocytes in their native tissue (tissue extracts) and during culture (conditioned media day 7, both nonexpanded and expanded chondrocytes), cytokine production was evaluated per DNA in samples from healthy cartilage, debrided cartilage from defects and osteoarthritic cartilage. Results are represented as mean ± standard deviation. Differences in cytokine levels between healthy, cartilage defect and OA donors were determined using the Kruskall–Wallis test (P values shown in table) with post hoc Mann–Whitney U test: tissue – VEGF: H vs. CD, P = 0.002; H vs. OA, P = 0.024; CD vs. OA, P = 0.002; unexpanded chondrocytes – IL-1β: H vs. CD, P <0.001; H vs. OA, P = 0.002; CD vs. OA, P = 0.013; expanded chondrocytes – IL-6: H vs. CD, P <0.001; H vs. OA, P <0.001; CD vs. OA, P <0.001; IL-8: H vs. OA, P <0.001; CD vs. OA, P <0.001; H vs. OA, P = 0.008; CD vs. OA, P <0.001. bFGF, basic fibroblast growth factor; CD, cartilage defect; H, healthy; HGF, hepatocyte growth factor; IFNγ, interferon gamma; IL, interleukin; LIF, leukaemia inhibitory factor; MCP1, monocyte chemotactic factor 1; OA, osteoarthritis; OSM, oncostatin M; RANTES, regulated upon activation normal T cell expressed and presumably secreted; TNFα, tumour necrosis factor alpha; VEGF, vascular endothelial growth factor. *P <0.001.