0 12 Differential differential JJ 13 23 inhibition inhibition NN 24 26 of of IN 27 32 Smad6 Smad6 NNP 33 36 and and CC 37 42 Smad7 Smad7 NNP 43 45 on on IN 46 50 bone bone NN 51 64 morphogenetic morphogenetic JJ 65 73 protein- protein- NN 74 77 and and CC 78 94 activin-mediated activin-mediated JJ 95 101 growth growth NN 102 108 arrest arrest NN 109 112 and and CC 113 122 apoptosis apoptosis NN 123 125 in in IN 126 127 B B NNP 128 133 cells cell NNS 133 134 . . . 136 141 Smad6 Smad6 NNP 142 145 and and CC 146 151 Smad7 Smad7 NNP 152 159 prevent prevent VBP 160 174 ligand-induced ligand-induced JJ 175 185 activation activation NN 186 188 of of IN 189 207 signal-transducing signal-transducing JJ 208 212 Smad smad NN 213 221 proteins protein NNS 222 224 in in IN 225 228 the the DT 229 241 transforming transform VBG 242 248 growth growth NN 249 260 factor-beta factor-beta NN 261 267 family family NN 267 268 . . . 269 273 Here here RB 274 276 we we PRP 277 288 demonstrate demonstrate VBP 289 293 that that IN 294 298 both both CC 299 304 Smad6 Smad6 NNP 305 308 and and CC 309 314 Smad7 Smad7 NNP 315 318 are be VBP 319 324 human human JJ 325 329 bone bone NN 330 343 morphogenetic morphogenetic JJ 344 353 protein-2 protein-2 NN 354 355 ( ( ( 355 372 hBMP-2)-inducible hbmp-2)-inducible JJ 373 384 antagonists antagonist NNS 385 387 of of IN 388 402 hBMP-2-induced hbmp-2-induced JJ 403 409 growth growth NN 410 416 arrest arrest NN 417 420 and and CC 421 430 apoptosis apoptosis NN 431 433 in in IN 434 439 mouse mouse NN 440 441 B B NNP 442 446 cell cell NN 447 456 hybridoma hybridoma NN 457 462 HS-72 hs-72 NN 463 468 cells cell NNS 468 469 . . . 470 478 Moreover moreover RB 478 479 , , , 480 482 we we PRP 483 492 confirmed confirm VBD 493 497 that that IN 498 501 the the DT 502 509 ectopic ectopic JJ 510 521 expressions expression NNS 522 524 of of IN 525 530 Smad6 Smad6 NNP 531 534 and and CC 535 540 Smad7 Smad7 NNP 541 550 inhibited inhibit VBD 551 554 the the DT 555 569 hBMP-2-induced hbmp-2-induced JJ 570 581 Smad1/Smad5 smad1/smad5 NN 582 597 phosphorylation phosphorylation NN 597 598 . . . 599 601 We we PRP 602 612 previously previously RB 613 621 reported report VBD 622 626 that that IN 627 632 Smad7 smad7 NN 633 635 is be VBZ 636 638 an an DT 639 646 activin activin NN 647 658 A-inducible a-inducible JJ 659 669 antagonist antagonist NN 670 672 of of IN 673 680 activin activin NN 681 690 A-induced a-induced JJ 691 697 growth growth NN 698 704 arrest arrest NN 705 708 and and CC 709 718 apoptosis apoptosis NN 719 721 in in IN 722 727 HS-72 hs-72 NN 728 733 cells cell NNS 733 734 . . . 735 748 Interestingly interestingly RB 748 749 , , , 750 758 although although IN 759 763 mRNA mrna NN 764 774 expression expression NN 775 777 of of IN 778 783 Smad6 Smad6 NNP 784 787 was be VBD 788 795 induced induce VBN 796 798 by by IN 799 806 activin activin NN 807 808 A a NN 809 811 in in IN 812 817 HS-72 hs-72 NN 818 823 cells cell NNS 823 824 , , , 825 830 Smad6 Smad6 NNP 831 837 showed show VBD 838 840 no no DT 841 853 antagonistic antagonistic JJ 854 860 effect effect NN 861 863 on on IN 864 871 activin activin NN 872 881 A-induced a-induced JJ 882 888 growth growth NN 889 895 arrest arrest NN 896 899 and and CC 900 909 apoptosis apoptosis NN 909 910 . . . 911 919 Moreover moreover RB 919 920 , , , 921 923 we we PRP 924 929 found find VBD 930 934 that that IN 935 938 the the DT 939 946 ectopic ectopic JJ 947 957 expression expression NN 958 960 of of IN 961 966 Smad7 smad7 NN 966 967 , , , 968 971 but but CC 972 975 not not RB 976 981 Smad6 Smad6 NNP 981 982 , , , 983 992 inhibited inhibit VBD 993 996 the the DT 997 1004 activin activin NN 1005 1014 A-induced a-induced JJ 1015 1020 Smad2 smad2 NN 1021 1036 phosphorylation phosphorylation NN 1037 1039 in in IN 1040 1045 HS-72 hs-72 NN 1046 1051 cells cell NNS 1051 1052 . . . 1053 1057 Thus thus RB 1057 1058 , , , 1059 1064 Smad6 Smad6 NNP 1065 1068 and and CC 1069 1074 Smad7 Smad7 NNP 1075 1082 exhibit exhibit VBP 1083 1095 differential differential JJ 1096 1106 inhibitory inhibitory JJ 1107 1114 effects effect NNS 1115 1117 in in IN 1118 1122 bone bone NN 1123 1136 morphogenetic morphogenetic JJ 1137 1147 protein-2- protein-2- NN 1148 1151 and and CC 1152 1159 activin activin NN 1160 1170 A-mediated a-mediated JJ 1171 1180 signaling signaling NN 1181 1183 in in IN 1184 1185 B B NNP 1186 1193 lineage lineage NN 1194 1199 cells cell NNS 1199 1200 . . .