0 13 Cross-linking cross-linking NN 14 16 of of IN 17 21 CD44 cd44 NN 22 24 on on IN 25 35 rheumatoid rheumatoid JJ 36 44 synovial synovial JJ 45 50 cells cell NNS 51 63 up-regulates up-regulate VBZ 64 70 VCAM-1 vcam-1 NN 70 71 . . . 73 77 CD44 CD44 NNP 78 80 is be VBZ 81 82 a a DT 83 93 ubiquitous ubiquitous JJ 94 102 molecule molecule NN 103 107 also also RB 108 113 known know VBN 114 116 as as IN 117 127 hyaluronic hyaluronic JJ 128 132 acid acid NN 133 135 or or CC 136 142 homing homing JJ 143 151 receptor receptor NN 151 152 . . . 153 160 However however RB 160 161 , , , 162 165 the the DT 166 174 cellular cellular JJ 175 184 functions function NNS 185 188 and and CC 189 192 its its PRP$ 193 197 role role NN 198 200 in in IN 201 213 inflammation inflammation NN 213 214 , , , 215 218 for for IN 219 226 example example NN 226 227 , , , 228 238 rheumatoid rheumatoid JJ 239 248 synovitis synovitis NN 248 249 , , , 250 253 are be VBP 254 263 currently currently RB 264 271 unknown unknown JJ 271 272 . . . 273 275 In in IN 276 280 this this DT 281 286 study study NN 286 287 , , , 288 290 we we PRP 291 298 propose propose VBP 299 300 a a DT 301 306 novel novel JJ 307 315 function function NN 316 319 for for IN 320 324 CD44 cd44 NN 324 325 . . . 326 331 Using use VBG 332 340 synovial synovial JJ 341 346 cells cell NNS 347 351 from from IN 352 362 rheumatoid rheumatoid JJ 363 372 arthritis arthritis NN 373 374 ( ( ( 374 376 RA RA NNP 376 377 ) ) ) 378 386 patients patient NNS 386 387 , , , 388 390 we we PRP 391 403 demonstrated demonstrate VBD 404 408 that that IN 409 413 CD44 cd44 NN 414 427 cross-linking cross-linking NN 428 431 and and CC 432 439 binding binding NN 440 442 to to TO 443 453 hyaluronan hyaluronan NN 454 463 augmented augment VBD 464 470 VCAM-1 vcam-1 NN 471 481 expression expression NN 482 485 and and CC 486 498 subsequently subsequently RB 499 514 VCAM-1-mediated vcam-1-mediated JJ 515 519 cell cell NN 520 528 adhesion adhesion NN 528 529 . . . 530 537 Briefly briefly RB 537 538 , , , 539 541 we we PRP 542 547 found find VBD 548 552 that that IN 553 554 1 1 LS 554 555 ) ) ) 556 566 rheumatoid rheumatoid JJ 567 575 synovial synovial JJ 576 581 cells cell NNS 582 588 highly highly RB 589 598 expressed express VBD 599 603 CD44 cd44 NN 603 604 ; ; : 605 606 2 2 LS 606 607 ) ) ) 608 621 cross-linking cross-linking NN 622 624 of of IN 625 629 CD44 cd44 NN 630 638 markedly markedly RB 639 642 but but CC 643 654 transiently transiently RB 655 664 augmented augment VBD 665 671 VCAM-1 vcam-1 NN 672 682 expression expression NN 683 686 and and CC 687 690 its its PRP$ 691 695 mRNA mrna NN 696 709 transcription transcription NN 710 714 much much RB 715 719 more more RBR 720 724 than than IN 725 728 did do VBD 729 737 IL-1beta IL-1beta NNP 738 741 and and CC 742 751 TNF-alpha TNF-alpha NNP 751 752 ; ; : 753 754 3 3 LS 754 755 ) ) ) 756 766 hyaluronan hyaluronan NN 766 767 , , , 768 778 especially especially RB 779 783 when when WRB 784 794 fragmented fragment VBN 794 795 , , , 796 800 also also RB 801 813 up-regulated up-regulate VBD 814 820 VCAM-1 vcam-1 NN 820 821 ; ; : 822 823 4 4 LS 823 824 ) ) ) 825 829 CD44 cd44 NN 830 839 activated activate VBD 840 843 the the DT 844 857 transcription transcription NN 858 864 factor factor NN 865 869 AP-1 ap-1 NN 869 870 ; ; : 871 874 and and CC 875 876 5 5 LS 876 877 ) ) ) 878 881 the the DT 882 900 integrin-dependent integrin-dependent JJ 901 909 adhesive adhesive JJ 910 918 function function NN 919 921 of of IN 922 924 RA RA NNP 925 933 synovial synovial JJ 934 939 cells cell NNS 940 942 to to TO 943 944 T t NN 945 950 cells cell NNS 951 954 was be VBD 955 959 also also RB 960 969 amplified amplify VBN 970 972 by by IN 973 977 CD44 cd44 NN 978 991 cross-linking cross-linking NN 991 992 . . . 993 998 These these DT 999 1006 results result NNS 1007 1015 indicate indicate VBP 1016 1020 that that IN 1021 1024 the the DT 1025 1033 adhesion adhesion NN 1034 1036 of of IN 1037 1039 RA RA NNP 1040 1048 synovial synovial JJ 1049 1054 cells cell NNS 1055 1057 to to TO 1058 1066 matrices matrix NNS 1067 1071 such such JJ 1072 1074 as as IN 1075 1085 hyaluronic hyaluronic JJ 1086 1090 acid acid NN 1091 1098 through through IN 1099 1103 CD44 cd44 NN 1104 1109 could could MD 1110 1121 up-regulate up-regulate VB 1122 1128 VCAM-1 vcam-1 NN 1129 1139 expression expression NN 1140 1143 and and CC 1144 1159 VCAM-1-mediated vcam-1-mediated JJ 1160 1168 adhesion adhesion NN 1169 1171 to to TO 1172 1173 T t NN 1174 1179 cells cell NNS 1179 1180 , , , 1181 1186 which which WDT 1187 1192 might might MD 1193 1195 in in IN 1196 1200 turn turn NN 1201 1206 cause cause VBP 1207 1217 activation activation NN 1218 1220 of of IN 1221 1222 T t NN 1223 1228 cells cell NNS 1229 1232 and and CC 1233 1241 synovial synovial JJ 1242 1247 cells cell NNS 1248 1250 in in IN 1251 1253 RA RA NNP 1254 1263 synovitis synovitis NNP 1263 1264 . . . 1265 1267 We we PRP 1268 1277 therefore therefore RB 1278 1285 propose propose VBP 1286 1290 that that IN 1291 1295 such such JJ 1296 1309 cross-talking cross-talking NN 1310 1315 among among IN 1316 1324 distinct distinct JJ 1325 1333 adhesion adhesion NN 1334 1343 molecules molecule NNS 1344 1347 may may MD 1348 1350 be be VB 1351 1359 involved involve VBN 1360 1362 in in IN 1363 1366 the the DT 1367 1379 pathogenesis pathogenesis NN 1380 1382 of of IN 1383 1395 inflammation inflammation NN 1395 1396 , , , 1397 1406 including include VBG 1407 1409 RA RA NNP 1410 1419 synovitis synovitis NN 1419 1420 . . .