Differentiation and activity of human primary osteoclasts from peripheral blood mononuclear cells under the influence of orthopedic wear particles

To date, the process of aseptic implant loosening of endoprosthesis is still the leading problem of total joint replacements and is mainly caused by particulate wear debris generated by mechanical loading and friction in articulating surfaces. Those particles trigger a multistep biological reaction which include several cell types of the periprosthetic tissue and result in induction of an inflammatory cascade and osteolysis. The influence of various types of wear particles on bone forming osteoblasts and on macrophages is well-investigated. However, the number of comparative studies dealing with differentiating and mature osteoclasts is restricted. So, in the present study human peripheral blood mononuclear cells were exposed to titanium and zirconium particles in different concentrations for several time points to evaluate particle influence on cell differentiation into osteoclasts and on morphology and functionality of mature osteoclasts.

• Establishment of osteoclast isolation from peripheral blood mononuclear cells from human buffy coats, cell differentiation and cultivation
• Exposure of differentiating and mature osteoclasts with metallic and ceramic wear particles in different concentrations for multiple points in time
• Determination of osteoclast specific genes, proteins and inflammatory markers; cell specific staining; cell size quantification; resorption assays; metabolic cell activity

Peer-reviewed journal papers:

MARKHOFF, J., PASOLD, J., TILLMANN, J., KROGULL, M., BADER, R., 2017. Influence of metallic and ceramic particles on the differentiation of human mononuclear cells into osteoclasts. (under review, Journal of Biomedical Materials Research: Part A)

PASOLD, J., MARKHOFF, J., TILLMANN, J., KROGULL, M., PISOWOCKI, P., BADER, R., 2017. Direct influence of titanium and zirconia particles on the morphology and functionality of mature human osteoclasts. (in revision, Journal of Biomedical Materials Research: Part A)

MARKHOFF, J., ZIETZ, C., FABRY, C., FULDA, G., BADER, R., 2017. Influence of analyzed lubricant volumes on the amount and characteristics of generated wear particles from three different types of polyethylene liner materials. (in revision, Journal of Biomedical Materials Research: Part B - Applied Biomaterials

KLINDER, A.*, MARKHOFF, J.*, PASOLD, J., STERNA, P., SALAMON, A., JONITZ-HEINCKE, A., BADER, R., 2017. Comparison of different cell culture dishes for the enrichment of non-adherent human mononuclear cells. (under review, Journal of Orthopaedic Research)

MARKHOFF, J., KROGULL, M., SCHULZE, C., ROTSCH, C., HUNGER, S., BADER, R., 2017. Biocompatibility and inflammatory potential of titanium alloys cultivated with human osteoblasts, fibroblasts and macrophages. Special Issue “Biocompatibility of Materials 2016”, Materials 2017, 10(1), 52 (17 pages). DOI: 10.3390/ma10010052.

MARKHOFF, J., WEINMANN, M., SCHULZE, C., BADER, R., 2017. Influence of different grained powders and pellets made of Niobium and Ti-42Nb on human cell viability. Materials Science and Engineering C, 73, pp. 756–766. DOI: 10.1016/j.msec.2016.12.098.

MARKHOFF, J., WIEDING, J., WEISSMANN, V., PASOLD, J., JONITZ-HEINCKE, A., BADER, R., 2015. Influence of different three-dimensional open porous titanium scaffold designs on human osteoblasts behavior in static and dynamic cell investigations. Materials 2015, 8(8), pp. 5490-5507. DOI:10.3390/ma8085259.

MARKHOFF, J., MICK, E., MITROVIC, A., PASOLD, J., WEGNER, K., BADER, R., 2014. Surface modifications of dental ceramic implants with different glass solder matrices: In vitro analyses with human primary osteoblasts and epithelial cells. Special Issue „Osteogenic Biomaterials in Contemporary Dentistry“, Biomed Research International. 2014:742180. DOI: 10.1155/2014/742180.

MICK, E., MARKHOFF, J., MITROVIC, A., JONITZ, A., BADER, R., 2013. New Coating Technique of Ceramic Implants with Different Glass Solder Matrices for Improved Osseointegration-Mechanical Investigations. Materials 2013, 6, pp. 4001-4010. DOI:10.3390/ma6094001.

MARKHOFF, J., JONITZ, A., ZIETZ, C., LOCHNER, K., HANSMANN, D., BADER, R., 2013. Establishment of a novel in vitro test setup exposing adherent cells to wear particles made of polyethylene. Polymer Testing, 32(5), pp. 982-986. DOI: 10.1016/j.polymertesting.2013.05.005

Peer-reviewed paper important congresses:

PASOLD, J., MARKHOFF, J., TILLMANN, J., PISOWOCKI, P., BADER, R., 2016. Exposure to Metallic and Ceramic Wear Particles Leads to an Increased Osteoclast Activation and Fusion. 62th Annual Meeting of the Orthopaedic Research Society, Poster, Orlando, FL, USA.

PASOLD, J., MARKHOFF, J., TILLMANN, J., BADER, R., 2015. The functional properties of human mature osteoclasts are influenced by phagocytosis of metallic and ceramic wear particles. 19. Chirurgische Forschungstage, Lecture, Wuerzburg, Germany.

MARKHOFF, J., PASOLD, J., TILLMANN, J., BADER, R., 2015. Influence of metallic and ceramic wear particles on differentiation and functionality of human osteoclasts. International Conference on Tissue Engineering (ICTE), Lecture, Lisbon, Portugal.

MARKHOFF, J., PASOLD, J., HESKAMP, B., STERNA, P., TILLMANN, J., SALAMON, A., HANSMANN, D., JONITZ-HEINCKE, A., BADER, R., 2014. Hydrophilic cell culture surfaces enable the enrichment of human mononuclear cells for subsequent exposure to metallic and ceramic particles. 18. Chirurgische Forschungstage, Lecture, Hanover, Germany.

MARKHOFF, J., HESKAMP, B., STERNA, P., JONITZ-HEINCKE, A., BADER, R. 2014. Cultivation of human mononuclear cells in modified cell culture plates to prevent adhesion-induced differentiation. Osteologie Kongress, Poster, Munich, Germany.

• Prof. Dr. Rainer Bader
• Prof. Dr. Barbara Nebe