0 10 Osteoclast Osteoclast NNP 11 18 markers marker NNS 19 29 accumulate accumulate VBP 30 32 on on IN 33 38 cells cell NNS 39 49 developing develop VBG 50 54 from from IN 55 60 human human JJ 61 71 peripheral peripheral JJ 72 77 blood blood NN 78 89 mononuclear mononuclear JJ 90 100 precursors precursor NNS 100 101 . . . 103 109 Recent recent JJ 110 117 studies study NNS 118 122 show show VBP 123 127 that that IN 128 133 human human JJ 134 145 osteoclasts osteoclast NNS 146 153 develop develop VBP 154 156 in in FW 157 162 vitro vitro FW 163 167 from from IN 168 181 hematopoietic hematopoietic JJ 182 187 cells cell NNS 187 188 ; ; : 189 196 however however RB 196 197 , , , 198 205 special special JJ 206 214 cultures culture NNS 215 225 conditions condition NNS 226 232 and/or and/or CC 233 241 cytokine cytokine NN 242 251 mobilized mobilize VBD 252 262 peripheral peripheral JJ 263 268 blood blood NN 269 272 are be VBP 273 283 apparently apparently RB 284 292 required require VBN 292 293 . . . 294 298 Here here RB 298 299 , , , 300 302 we we PRP 303 309 report report VBP 310 314 that that IN 315 320 cells cell NNS 321 331 expressing express VBG 332 342 osteoclast osteoclast NN 343 350 markers marker NNS 351 364 differentiate differentiate VBP 365 369 from from IN 370 380 precursors precursor NNS 381 388 present present JJ 389 391 in in IN 392 404 nonmobilized nonmobilized JJ 405 415 peripheral peripheral JJ 416 421 blood blood NN 422 433 mononuclear mononuclear JJ 434 439 cells cell NNS 440 441 ( ( ( 441 445 PBMC PBMC NNP 445 446 ) ) ) 446 447 , , , 448 455 without without IN 456 459 the the DT 460 468 addition addition NN 469 471 of of IN 472 479 stromal stromal JJ 480 485 cells cell NNS 485 486 , , , 487 493 growth growth NN 494 501 factors factor NNS 501 502 , , , 503 512 cytokines cytokine NNS 513 515 or or CC 516 524 steroids steroid NNS 524 525 ; ; : 526 529 and and CC 530 542 characterize characterize VBP 543 548 their their PRP$ 549 558 phenotype phenotype NN 558 559 . . . 560 565 Three three CD 566 570 days day NNS 571 576 after after IN 577 589 establishing establish VBG 590 602 high-density high-density JJ 603 607 PBMC PBMC NNP 608 616 cultures culture NNS 617 618 ( ( ( 618 621 1.5 1.5 CD 622 623 x x CC 624 629 10(6) 10(6) CD 630 639 cells/cm2 cells/cm2 NNS 639 640 ) ) ) 640 641 , , , 642 644 in in IN 645 661 serum-containing serum-containing JJ 662 668 medium medium NN 668 669 , , , 670 675 small small JJ 676 684 adherent adherent JJ 685 693 colonies colony NNS 694 696 of of IN 697 705 tartrate tartrate NN 706 715 resistant resistant JJ 716 720 acid acid NN 721 732 phosphatase phosphatase NN 733 741 positive positive JJ 742 743 ( ( ( 743 748 TRAP+ trap+ JJ 748 749 ) ) ) 750 755 cells cell NNS 756 762 emerge emerge VBP 762 763 , , , 764 770 amidst amidst IN 771 778 massive massive JJ 779 787 monocyte monocyte NN 788 792 cell cell NN 793 798 death death NN 798 799 . . . 800 805 These these DT 806 814 adherent adherent JJ 815 820 cells cell NNS 821 825 have have VBP 826 828 an an DT 829 842 eccentrically eccentrically RB 843 849 placed place VBN 849 850 , , , 851 856 round round JJ 857 864 nucleus nucleus NN 864 865 , , , 866 869 and and CC 870 877 express express VB 878 881 low low JJ 882 888 levels level NNS 889 891 of of IN 892 896 TRAP TRAP NNP 897 900 and and CC 901 907 sodium sodium NN 908 927 fluoride-resistant- fluoride-resistant- NN 928 959 alpha-naphthyl-acetate-esterase alpha-naphthyl-acetate-esterase NN 960 961 ( ( ( 961 970 NaF-R-NSE NaF-R-NSE NNP 970 971 ) ) ) 971 972 . . . 973 977 Over over IN 978 981 the the DT 982 986 next next JJ 987 991 week week NN 991 992 , , , 993 997 this this DT 998 1002 cell cell NN 1003 1013 population population NN 1014 1025 accumulates accumulate VBZ 1026 1036 phenotypic phenotypic JJ 1037 1044 markers marker NNS 1045 1047 of of IN 1048 1059 osteoclasts osteoclast NNS 1060 1061 ( ( ( 1061 1072 vitronectin vitronectin NN 1073 1081 receptor receptor NN 1082 1083 [ [ ( 1083 1085 VR VR NNP 1085 1086 ] ] ) 1086 1087 , , , 1088 1098 calcitonin calcitonin NN 1099 1107 receptor receptor NN 1107 1108 , , , 1109 1113 TRAP TRAP NNP 1113 1114 , , , 1115 1124 cathepsin cathepsin NN 1125 1126 K K NNP 1127 1134 protein protein NN 1134 1135 , , , 1136 1139 and and CC 1140 1144 mRNA mRNA NNP 1144 1145 ) ) ) 1146 1150 with with IN 1151 1160 increased increase VBN 1161 1171 nuclearity nuclearity NN 1171 1172 , , , 1173 1181 covering cover VBG 1182 1185 the the DT 1186 1192 entire entire JJ 1193 1200 surface surface NN 1201 1203 by by IN 1204 1206 15 15 CD 1207 1211 days day NNS 1211 1212 . . . 1213 1217 When when WRB 1218 1226 cultured culture VBN 1227 1229 on on IN 1230 1234 bone bone NN 1234 1235 , , , 1236 1239 VR+ vr+ JJ 1239 1240 , , , 1241 1246 TRAP+ trap+ JJ 1247 1252 cells cell NNS 1253 1255 of of IN 1256 1259 low low JJ 1260 1275 multinuclearity multinuclearity NN 1276 1282 appear appear VBP 1283 1286 and and CC 1287 1292 cover cover VBP 1293 1295 up up RB 1296 1298 to to TO 1299 1301 50 50 CD 1301 1302 % % NN 1303 1305 of of IN 1306 1309 the the DT 1310 1317 surface surface NN 1317 1318 . . . 1319 1329 Resorption Resorption NNP 1330 1337 lacunae lacuna NNS 1338 1341 can can MD 1342 1344 be be VB 1345 1353 observed observe VBN 1354 1356 by by IN 1357 1360 day day NN 1361 1363 22 22 CD 1363 1364 . . . 1365 1373 Although although IN 1374 1379 these these DT 1380 1384 pits pit NNS 1385 1388 are be VBP 1389 1392 not not RB 1393 1399 nearly nearly RB 1400 1402 as as RB 1403 1411 numerous numerous JJ 1412 1414 as as IN 1415 1418 the the DT 1419 1424 cells cell NNS 1425 1427 of of IN 1428 1441 preosteoclast preosteoclast NN 1442 1451 phenotype phenotype NN 1451 1452 , , , 1453 1457 they they PRP 1458 1460 do do VBP 1461 1470 represent represent VB 1471 1474 the the DT 1475 1483 activity activity NN 1484 1486 of of IN 1487 1488 a a DT 1489 1495 subset subset NN 1496 1498 of of IN 1499 1514 osteoclast-like osteoclast-like JJ 1515 1520 cells cell NNS 1521 1525 that that WDT 1526 1529 has have VBZ 1530 1538 achieved achieve VBN 1539 1551 osteoclastic osteoclastic JJ 1552 1560 maturity maturity NN 1561 1566 under under IN 1567 1572 these these DT 1573 1580 culture culture NN 1581 1591 conditions condition NNS 1591 1592 . . . 1593 1604 Transcripts transcript NNS 1605 1608 for for IN 1609 1624 osteoprotegerin osteoprotegerin NN 1625 1631 ligand ligand NN 1632 1633 ( ( ( 1633 1637 OPGL OPGL NNP 1637 1638 ) ) ) 1638 1639 , , , 1640 1642 an an DT 1643 1653 osteoclast osteoclast NN 1654 1669 differentiation differentiation NN 1670 1676 factor factor NN 1677 1678 ( ( ( 1678 1682 also also RB 1683 1688 known know VBN 1689 1691 as as IN 1692 1697 RANKL RANKL NNP 1698 1701 and and CC 1702 1708 TRANCE TRANCE NNP 1708 1709 ) ) ) 1710 1713 are be VBP 1714 1723 expressed express VBN 1723 1724 , , , 1725 1731 likely likely RB 1732 1734 by by IN 1735 1743 adherent adherent JJ 1744 1749 cells cell NNS 1749 1750 . . . 1751 1755 Thus thus RB 1755 1756 , , , 1757 1759 an an DT 1760 1768 adherent adherent JJ 1769 1779 population population NN 1780 1782 of of IN 1783 1788 cells cell NNS 1788 1789 , , , 1790 1794 with with IN 1795 1819 preosteoclast/osteoclast preosteoclast/osteoclast JJ 1820 1830 phenotypic phenotypic JJ 1831 1841 properties property NNS 1841 1842 , , , 1843 1849 arises arise VBZ 1850 1861 selectively selectively RB 1862 1867 under under IN 1868 1874 simple simple JJ 1875 1882 culture culture NN 1883 1893 conditions condition NNS 1894 1898 from from IN 1899 1905 normal normal JJ 1906 1910 PBMC PBMC NNP 1910 1911 . . . 1912 1919 Further further JJ 1920 1936 characterization characterization NN 1937 1939 of of IN 1940 1945 these these DT 1946 1951 cells cell NNS 1952 1958 should should MD 1959 1967 identify identify VB 1968 1975 factors factor NNS 1976 1984 involved involve VBN 1985 1987 in in IN 1988 1991 the the DT 1992 1998 growth growth NN 1998 1999 , , , 2000 2008 terminal terminal JJ 2009 2024 differentiation differentiation NN 2025 2028 and and CC 2029 2039 activation activation NN 2040 2042 of of IN 2043 2054 osteoclasts osteoclast NNS 2054 2055 . . .