title: Aggravation of inflammatory response by costimulation with titanium particles and mechanical perturbations in osteoblast- and macrophage-like cells.
abstract: The interface between bone tissue and metal implants undergoes various types of mechanical loading, such as strain, compression, fluid pressure, and shear stress, from daily activities. Such mechanical perturbations create suboptimal environments at the host bone-implant junction, causing an accumulation of wear particles and debilitating osseous integration, potentially leading to implant failure. While many studies have focused on the effect of particles on macrophages or osteoprogenitor cells, differential and combined effects of mechanical perturbations and particles on such cell types have not been extensively studied. In this study, macrophages and osteoprogenitor cells were subjected to physiological and superphysiological mechanical stimuli in the presence and absence of Ti particles with the aim of simulating various microenvironments of the host bone-implant junction. Macrophages and osteoprogenitor cells were capable of engulfing Ti particles through actin remodeling and also exhibited changes in mRNA levels of proinflammatory cytokines under certain conditions. In osteoprogenitor cells, superphysiological strain increased proinflammatory gene expression; in macrophages, such mechanical perturbations did not affect gene expression. We confirmed that this phenomenon in osteoprogenitor cells occurred via activation of the ERK1/2 signaling pathway as a result of damage to the cytoplasmic membrane. Furthermore, AZD6244, a clinically relevant inhibitor of the ERK1/2 pathway, mitigated particle-induced inflammatory gene expression in osteoprogenitor cells and macrophages. This study provides evidence of more inflammatory responses under mechanical strains in osteoprogenitor cells than macrophages. Phagocytosis of particles and mechanical perturbation costimulate the ERK1/2 pathway, leading to expression of proinflammatory genes.
authors.affiliation: Center for Orthopaedic Research, Columbia Orthopaedics, Department of Orthopaedic Surgery, Columbia University College of Physicians and Surgeons, New York, NY 10032, USA.
authors.forename: Heon Goo
authors.initials: HG
authors.lastname: Lee
authors.forename: Anny
authors.initials: A
authors.lastname: Hsu
authors.forename: Hana
authors.initials: H
authors.lastname: Goto
authors.forename: Saqib
authors.initials: S
authors.lastname: Nizami
authors.forename: Jonathan H
authors.initials: JH
authors.lastname: Lee
authors.forename: Edwin R
authors.initials: ER
authors.lastname: Cadet
authors.forename: Peter
authors.initials: P
authors.lastname: Tang
authors.forename: Roya
authors.initials: R
authors.lastname: Shaji
authors.forename: Chandhanarat
authors.initials: C
authors.lastname: Chandhanayinyong
authors.forename: Seok Hyun
authors.initials: SH
authors.lastname: Kweon
authors.forename: Daniel S
authors.initials: DS
authors.lastname: Oh
authors.forename: Hesham
authors.initials: H
authors.lastname: Tawfeek
authors.forename: Francis Y
authors.initials: FY
authors.lastname: Lee
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D002460:Cell Line; D002462:Cell Membrane / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D060833:Cellular Microenvironment / Q000187:drug effects / Q000235:genetics; D016207:Cytokines / Q000235:genetics / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D007249:Inflammation / Q000139:chemically induced* / Q000235:genetics* / Q000378:metabolism; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000235:genetics; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism; D010587:Phagocytosis / Q000187:drug effects / Q000235:genetics; D019736:Prostheses and Implants; D014025:Titanium / Q000633:toxicity*
chemical_list: D000199:Actins; D016207:Cytokines; D014025:Titanium