RESUMEN
The cytokines secreted by immune cells have a large impact on the tissue, surrounding a fracture, e.g., by attraction of osteoprogenitor cells. However, the underlying mechanisms are not yet fully understood. Thus, this study aims at investigating molecular mechanisms of the immune cell-mediated migration of immature primary human osteoblasts (phOBs), with transforming growth factor beta (TGF-ß), nicotinamide adenine dinucleotide phosphate (NADPH) oxidase 4 (NOX4) and focal adhesion kinase (FAK) as possible regulators. Monocyte- and macrophage (THP-1 cells ± phorbol 12-myristate 13-acetate (PMA) treatment)-conditioned media, other than the granulocyte-conditioned medium (HL-60 cells + dimethyl sulfoxide (DMSO) treatment), induce migration of phOBs. Monocyte- and macrophage (THP-1 cells)-conditioned media activate Smad3-dependent TGF-ß signaling in the phOBs. Stimulation with TGF-ß promotes migration of phOBs. Furthermore, TGF-ß treatment strongly induces NOX4 expression on both mRNA and protein levels. The associated reactive oxygen species (ROS) accumulation results in phosphorylation (Y397) of FAK. Blocking TGF-ß signaling, NOX4 activity and FAK signaling effectively inhibits the migration of phOBs towards TGF-ß. In summary, our data suggest that monocytic- and macrophage-like cells induce migration of phOBs in a TGF-ß-dependent manner, with TGF-ß-dependent induction of NOX4, associated production of ROS and resulting activation of FAK as key mediators.
Asunto(s)
Proteína-Tirosina Quinasas de Adhesión Focal/metabolismo , NADPH Oxidasa 4/metabolismo , Factor de Crecimiento Transformador beta/metabolismo , Diferenciación Celular/efectos de los fármacos , Movimiento Celular/efectos de los fármacos , Células Cultivadas , Células HL-60 , Humanos , Fosforilación/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Transducción de Señal/efectos de los fármacos , Células THP-1 , Acetato de Tetradecanoilforbol/análogos & derivados , Acetato de Tetradecanoilforbol/farmacologíaRESUMEN
PURPOSE: The objective of the present study was to explore the effect of navigation on the reconstruction of the mechanical leg axis, implant positioning and the restoration of the joint line in hinged knee arthroplasty in vivo. We present the first 1- to 3-year clinical and radiological results following computer-navigated implantation of the EnduRo modular rotating-hinge knee arthroplasty system (Aesculap AG, Tuttlingen, Germany) as a primary or revision implant. METHODS: Thirty-one patients were analysed retrospectively. Indication was revision surgery in 18 patients and complex primary surgery in 13. The clinical and radiological results of 31 patients with a minimum follow-up of 12 months (mean 22.2 ± 6.2 months) were recorded. Age at follow-up was 55.2 ± 9.9 years. RESULTS: The absolute varus-valgus deviation from the neutral mechanical leg axis was determined at 5.1° ± 5.1° preoperatively and 2.1° ± 1.4° postoperatively. No intraoperative complications or problems with the navigation system were observed. At latest follow-up, no component loosening was detected. Based on the Knee Society Score, a knee score of 64.9 ± 17.7 points and a function score of 67.2 ± 27.3 points were achieved. CONCLUSIONS: Encouraging short-term clinical and radiological results with the computer-navigated implantation of the modular rotating-hinge EnduRo knee arthroplasty system were found in both primary and revision surgery. The navigation facilitated the reconstruction of the leg axis, implant positioning and the restoration of the joint line. LEVEL OF EVIDENCE: IV.