title: Effects of titanium particle size on osteoblast functions in vitro and in vivo.
abstract: 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-bone 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 in vivo, 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 in vivo. This study demonstrates the significant attenuation of osteoblast function concurrent with increased expression of receptor activator of nuclear factor kappaB 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.
authors.affiliation: Department of Orthopedic Surgery, University of California at San Diego, 9500 Gilman Drive, La Jolla, CA 92093, USA.
authors.forename: Moon G
authors.initials: MG
authors.lastname: Choi
authors.forename: Hae S
authors.initials: HS
authors.lastname: Koh
authors.forename: Daniel
authors.initials: D
authors.lastname: Kluess
authors.forename: Daniel
authors.initials: D
authors.lastname: O'Connor
authors.forename: Anshu
authors.initials: A
authors.lastname: Mathur
authors.forename: George A
authors.initials: GA
authors.lastname: Truskey
authors.forename: Janet
authors.initials: J
authors.lastname: Rubin
authors.forename: David X F
authors.initials: DX
authors.lastname: Zhou
authors.forename: K-L Paul
authors.initials: KL
authors.lastname: Sung
mesh_terms: D000818:Animals; D001696:Biomechanical Phenomena; D001858:Bone Nails; D002352:Carrier Proteins / Q000235:genetics; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D066298:In Vitro Techniques; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D008562:Membrane Glycoproteins / Q000235:genetics; D016348:Osseointegration / Q000187:drug effects / Q000235:genetics / Q000502:physiology; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology*; D010316:Particle Size; D011475:Prosthesis Failure; D053245:RANK Ligand; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013977:Tibia / Q000166:cytology / Q000601:surgery; D014025:Titanium / Q000008:administration & dosage / Q000633:toxicity*
chemical_list: D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D053245:RANK Ligand; D012333:RNA, Messenger; D014025:Titanium; D020778:Matrix Metalloproteinase 2; D020780:Matrix Metalloproteinase 9