title: Exogenous MC3T3 preosteoblasts migrate systemically and mitigate the adverse effects of wear particles.
abstract: Understanding how relevant cell types respond to wear particles will reveal new avenues for treating osteolysis following joint replacements. In this study, we investigate the effects of ultrahigh molecular weight polyethylene (UHMWPE) particles on preosteoblast migration and function. We infused UHMWPE particles or saline into the left femur of mice and injected luciferase-expressing preosteoblasts (MC3T3 cells) into each left ventricle. Bioluminescence imaging (BLI) confirmed systemic administration of MC3T3 cells. BLI throughout the 28-day experiment showed greater MC3T3 migration to the site of particle infusion than to the site of saline infusion, with significant differences on days 0, 4, and 6 (p≤0.055). Immunostaining revealed a greater number of osteoblasts and osteoclasts in the particle-infused femora, indicating greater bone turnover. The bone mineralization of the particle-infused femora increased significantly when compared to saline-infused femora (an increase of 146.4±27.9 vs. 12.8±8.7 mg/mL, p=0.008). These results show that infused preosteoblasts can migrate to the site of wear particles. Additionally, as the migrated cells were associated with increased bone mineralization in spite of the presence of particles, increasing osteoblast recruitment is a potential strategy for combating bone loss due to increased osteoclast/macrophage number and decreased osteoblast function.
authors: Department of Orthopaedic Surgery, Stanford University School of Medicine, Stanford, California, USA.
authors: Kate
authors: K
authors: Fritton
authors: Pei-Gen
authors: PG
authors: Ren
authors: Emmanuel
authors: E
authors: Gibon
authors: Allison J
authors: AJ
authors: Rao
authors: Ting
authors: T
authors: Ma
authors: Sandip
authors: S
authors: Biswal
authors: Sanjiv S
authors: SS
authors: Gambhir
authors: Stuart B
authors: SB
authors: Goodman
mesh_terms: D000818:Animals; D002113:Calcification, Physiologic / Q000502:physiology*; D058948:Cell Tracking; D002633:Chemotaxis / Q000502:physiology*; D005269:Femur / Q000000981:diagnostic imaging / Q000293:injuries / Q000473:pathology / Q000601:surgery*; D017930:Genes, Reporter; D006352:Heart Ventricles; D007263:Infusions, Parenteral; D007267:Injections; D008163:Luminescent Measurements; D008297:Male; D051379:Mice; D008819:Mice, Nude; D010006:Osteoblasts / Q000166:cytology / Q000637:transplantation*; D010010:Osteoclasts / Q000166:cytology; D010316:Particle Size; D011095:Polyethylenes / Q000008:administration & dosage / Q000633:toxicity*; D014945:Wound Healing / Q000502:physiology*; D055114:X-Ray Microtomography
chemical_list: D011095:Polyethylenes; C111601:ultra-high molecular weight polyethylene