{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T07:03:34Z","timestamp":1789196614271,"version":"build-2803163510"},"reference-count":45,"publisher":"National Academy of Sciences","issue":"12","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2005,3,22]]},"abstract":"<jats:p>\n                    The formation of titanium (Ti)-wear particles during the lifetime of an implant is believed to be a major component of loosening due to debris-induced changes in bone cell function. Radiographic evidence indicates a loss of fixation at the implant\u2013bone interface, and we believe that the accumulation of Ti particles may act on the bone-remodeling process and impact both long- and short-term implant-fixation strengths. To determine the effects of various sizes of the Ti particles on osteoblast function\n                    <jats:italic>in vivo<\/jats:italic>\n                    , we measured the loss of integration strength around Ti-pin implants inserted into a rat tibia in conjunction with Ti particles from one of four size-groups. Implant integration is mediated primarily by osteoblast adhesion\/focal contact pattern, viability, proliferation and differentiation, and osteoclast recruitment at the implant site\n                    <jats:italic>in vivo<\/jats:italic>\n                    . This study demonstrates the significant attenuation of osteoblast function concurrent with increased expression of receptor activator of nuclear factor \u03baB ligand (RANKL), a dominant signal for osteoclast recruitment, which is regulated differentially, depending on the size of the Ti particle. Zymography studies have also demonstrated increased activities of matrix metalloproteinases (MMP) 2 and 9 in cells exposed to larger Ti particles. In summary, all particles have adverse effects on osteoblast function, resulting in decreased bone formation and integration, but different mechanisms are elicited by particles of different sizes.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0500693102","type":"journal-article","created":{"date-parts":[[2005,3,8]],"date-time":"2005-03-08T22:43:31Z","timestamp":1110321811000},"page":"4578-4583","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":97,"title":["Effects of titanium particle size on osteoblast functions\n                    <i>in vitro<\/i>\n                    and\n                    <i>in vivo<\/i>"],"prefix":"10.1073","volume":"102","author":[{"given":"Moon G.","family":"Choi","sequence":"first","affiliation":[{"name":"Departments of Orthopedic Surgery and Bioengineering and The Whitaker Institute of Biomedical Engineering, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093; Department of Biomedical Engineering, Duke University, Durham, NC 27708; and Department of Medicine, Emory University School of Medicine and Veterans Affairs Medical Center, Atlanta, GA 30033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hae S.","family":"Koh","sequence":"additional","affiliation":[{"name":"Departments of Orthopedic Surgery and Bioengineering and The Whitaker Institute of Biomedical Engineering, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093; Department of Biomedical Engineering, Duke University, Durham, NC 27708; and Department of Medicine, Emory University School of Medicine and Veterans Affairs Medical Center, Atlanta, GA 30033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"Kluess","sequence":"additional","affiliation":[{"name":"Departments of Orthopedic Surgery and Bioengineering and The Whitaker Institute of Biomedical Engineering, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093; Department of Biomedical Engineering, Duke University, Durham, NC 27708; and Department of Medicine, Emory University School of Medicine and Veterans Affairs Medical Center, Atlanta, GA 30033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel","family":"O'Connor","sequence":"additional","affiliation":[{"name":"Departments of Orthopedic Surgery and Bioengineering and The Whitaker Institute of Biomedical Engineering, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093; Department of Biomedical Engineering, Duke University, Durham, NC 27708; and Department of Medicine, Emory University School of Medicine and Veterans Affairs Medical Center, Atlanta, GA 30033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anshu","family":"Mathur","sequence":"additional","affiliation":[{"name":"Departments of Orthopedic Surgery and Bioengineering and The Whitaker Institute of Biomedical Engineering, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093; Department of Biomedical Engineering, Duke University, Durham, NC 27708; and Department of Medicine, Emory University School of Medicine and Veterans Affairs Medical Center, Atlanta, GA 30033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"George A.","family":"Truskey","sequence":"additional","affiliation":[{"name":"Departments of Orthopedic Surgery and Bioengineering and The Whitaker Institute of Biomedical Engineering, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093; Department of Biomedical Engineering, Duke University, Durham, NC 27708; and Department of Medicine, Emory University School of Medicine and Veterans Affairs Medical Center, Atlanta, GA 30033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Janet","family":"Rubin","sequence":"additional","affiliation":[{"name":"Departments of Orthopedic Surgery and Bioengineering and The Whitaker Institute of Biomedical Engineering, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093; Department of Biomedical Engineering, Duke University, Durham, NC 27708; and Department of Medicine, Emory University School of Medicine and Veterans Affairs Medical Center, Atlanta, GA 30033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David X. F.","family":"Zhou","sequence":"additional","affiliation":[{"name":"Departments of Orthopedic Surgery and Bioengineering and The Whitaker Institute of Biomedical Engineering, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093; Department of Biomedical Engineering, Duke University, Durham, NC 27708; and Department of Medicine, Emory University School of Medicine and Veterans Affairs Medical Center, Atlanta, GA 30033"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"K.-L. Paul","family":"Sung","sequence":"additional","affiliation":[{"name":"Departments of Orthopedic Surgery and Bioengineering and The Whitaker Institute of Biomedical Engineering, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093; Department of Biomedical Engineering, Duke University, Durham, NC 27708; and Department of Medicine, Emory University School of Medicine and Veterans Affairs Medical Center, Atlanta, GA 30033"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2005,3,8]]},"reference":[{"key":"e_1_3_2_1_2","first-page":"7","volume":"1144","year":"1992","unstructured":"Clarke, I. C., Campbell, P. & Kossovsky, N. (1992) Amer. Soc. Test. Mat. Spec. Tech. Pub. 1144, 7\u201326.","journal-title":"Amer. Soc. Test. Mat. Spec. Tech. Pub."},{"key":"e_1_3_2_2_2","doi-asserted-by":"crossref","first-page":"1086","DOI":"10.2106\/00004623-199307000-00017","volume":"75","year":"1993","unstructured":"Friedman, R. J., Black, J., Galante, J. O., Jacobs, J. J. & Skinner, H. B. (1993) J. Bone Jt. Surg. Am. Vol. 75A, 1086\u20131109.","journal-title":"J. Bone Jt. Surg. Am."},{"key":"e_1_3_2_3_2","first-page":"107","volume":"257","year":"1990","unstructured":"Engh, C. A., Massin, P. & Suthers, K. E. (1990) Clin. Orthop. Rel. Res. 257, 107\u2013128.","journal-title":"Clin. Orthop. Rel. Res."},{"key":"e_1_3_2_4_2","first-page":"583","volume":"79","year":"1997","unstructured":"Kobayashi, A., Donnelly, W. J., Scott, G. & Freeman, M. A. (1997) J. Bone Jt. Surg. Br. Vol. 79, 583\u2013589.","journal-title":"J. Bone Jt. Surg. Br."},{"key":"e_1_3_2_5_2","first-page":"980","volume":"72","year":"1990","unstructured":"Santavirta, S., Hoikka, V., Eskola, A., Knottinen, Y. T., Paavilainen, T. & Tallroth, K. (1990) J. Bone Jt. Surg. Br. Vol. 72, 980\u2013984.","journal-title":"J. Bone Jt. Surg. Br."},{"key":"e_1_3_2_6_2","first-page":"215","volume":"4","year":"1992","unstructured":"Wang, J. T., Harada, Y., Goldring, S. R. (1992) Sem. Arthroplasty 4, 215\u2013222.","journal-title":"Sem. Arthroplasty"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1002\/art.1780290704"},{"key":"e_1_3_2_8_2","first-page":"93","volume":"175","year":"1983","unstructured":"Linder, L., Lindberg, L. & Carlsson, A. (1983) Clin. Orthop. 175, 93\u2013104.6340903","journal-title":"Clin. Orthop."},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-198668030-00012"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1093\/rheumatology\/29.1.32"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1097\/00002281-199204000-00012"},{"key":"e_1_3_2_12_2","first-page":"S115","volume":"33","year":"1990","unstructured":"Bennett, N. E. & Goldring, S. R. (1990) Arthritis Rheum. 33, S115.","journal-title":"Arthritis Rheum."},{"key":"e_1_3_2_13_2","first-page":"209","volume":"264","year":"1991","unstructured":"Cook, S. D., McCluskey, L. C., Martin, P. C. & Haddad, R. J. (1991) Clin. Orthop. 264, 209\u2013222.1997238","journal-title":"Clin. Orthop."},{"key":"e_1_3_2_14_2","first-page":"90","volume":"234","year":"1988","unstructured":"Cook, S. D., Thomas, K. A. & Haddad, R. J. (1988) Clin. Orthop. 234, 90\u2013101.3409607","journal-title":"Clin. Orthop."},{"key":"e_1_3_2_15_2","first-page":"95","volume":"258","year":"1990","unstructured":"Willert, H. G., Bertram, H. & Buchhorn, B. H. (1990) Clin. Orthop. Rel. Res. 258, 95\u2013107.","journal-title":"Clin. Orthop. Rel. Res."},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002640000163"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.3928\/0147-7447-19840901-05"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.3109\/17453678108991775"},{"key":"e_1_3_2_19_2","first-page":"147","volume":"202","year":"1985","unstructured":"Cook, S. D., Scheller, A. D., Anderson, R. C. & Haddad, R. J. (1985) Clin. Orthop. 202, 147\u2013151.","journal-title":"Clin. Orthop."},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-198769090-00026"},{"key":"e_1_3_2_21_2","first-page":"303","volume":"236","year":"1988","unstructured":"Dohmae, Y., Bechtold, J. E., Sherman, R. E., Puno, R. M. & Gustilo, R. B. (1988) Clin. Orthop. 236, 303\u2013312.3052980","journal-title":"Clin. Orthop."},{"key":"e_1_3_2_22_2","first-page":"457","volume":"82","year":"2000","unstructured":"Urban, R. M., Jacobs, J. J., Tomlinson, M. J., Gavrilovic, J., Black, J. & Peoc'h, M. (2000) J. Bone Jt. Surg. Am. Vol. 82, 457\u2013476.","journal-title":"J. Bone Jt. Surg. Am."},{"key":"e_1_3_2_23_2","first-page":"406","volume":"9","year":"1993","unstructured":"Horowitz, S. M., Gautsh, T. L., Frondoza, C. G. & Riley, L., Jr. (1993) J. Orthop. Res. 9, 406\u2013413.","journal-title":"J. Orthop. Res."},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1007\/s002239900145"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1016\/0142-9612(96)00013-0"},{"key":"e_1_3_2_26_2","first-page":"496","volume":"63","year":"1988","unstructured":"Evans, C. E. & Jones, S. (1988) Calcif. Tissue Int. 63, 496\u2013504.","journal-title":"Calcif. Tissue Int."},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1002\/jor.1100180207"},{"key":"e_1_3_2_28_2","first-page":"161","volume":"38","year":"2001","unstructured":"Kwon, S. Y., Lin, T., Takei, H., Ma, Q., Wood, D. J., O'Connor, D. & Sung, K.-L. P. (2001) Biorheology 38, 161\u2013183.11381173","journal-title":"Biorheology"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-199701000-00011"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.139.3.5818"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1006\/abio.1999.4461"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2002-020656"},{"key":"e_1_3_2_33_2","doi-asserted-by":"publisher","DOI":"10.1359\/jbmr.2002.17.8.1452"},{"key":"e_1_3_2_34_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(20)89530-1"},{"key":"e_1_3_2_35_2","first-page":"27","volume":"2","year":"1996","unstructured":"Nugiel, D. J., Wood, D. & Sung, K.-L. P. (1996) Tissue Eng. 2, 27\u2013140.","journal-title":"Tissue Eng."},{"key":"e_1_3_2_36_2","doi-asserted-by":"publisher","DOI":"10.2106\/00004623-198971090-00009"},{"key":"e_1_3_2_37_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4636(19990905)46:3<399::AID-JBM13>3.0.CO;2-B"},{"key":"e_1_3_2_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0736-0266(03)00167-0"},{"key":"e_1_3_2_39_2","first-page":"108","volume":"333","year":"1996","unstructured":"Dorr, L. D., Hilton, K. R., Wan, Z, Markovich, G. D. & Bloebaum, R. (1996) Clin. Orthop. 333, 108\u2013117.8981886","journal-title":"Clin. Orthop."},{"key":"e_1_3_2_40_2","doi-asserted-by":"publisher","DOI":"10.1007\/s004020050213"},{"key":"e_1_3_2_41_2","doi-asserted-by":"publisher","DOI":"10.1902\/jop.2000.71.4.586"},{"key":"e_1_3_2_42_2","first-page":"683","volume":"124","year":"1997","unstructured":"Kadoya, Y., Salmivirta, K., Talts, J. F., Kadoya, K., Mayer, U., Timpl, R. & Ekblom, P. (1997) Development (Cambridge, U.K.) 124, 683\u2013691.","journal-title":"Development (Cambridge, U.K.)"},{"key":"e_1_3_2_43_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.95.7.3597"},{"key":"e_1_3_2_44_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.2000.3379"},{"key":"e_1_3_2_45_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.140.8.6887"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.0500693102","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,4,12]],"date-time":"2022-04-12T12:37:02Z","timestamp":1649767022000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.0500693102"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2005,3,8]]},"references-count":45,"journal-issue":{"issue":"12","published-print":{"date-parts":[[2005,3,22]]}},"alternative-id":["10.1073\/pnas.0500693102"],"URL":"https:\/\/doi.org\/10.1073\/pnas.0500693102","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2005,3,8]]},"assertion":[{"value":"2004-05-04","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2005-03-08","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}