Impact of Periprosthetic Fibroblast-Like Cells on Osteoclastogenesis in Co-Culture with Peripheral Blood Mononuclear Cells Varies Depending on Culture System

Miriam I Koehler, Eliza S Hartmann, Sabine Schluessel, Felicitas Beck, Julia I Redeker, Baerbel Schmitt, Marina Unger, Martijn van Griensven, Burkhard Summer, Andreas Fottner, Susanne Mayer-Wagner

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Co-culture studies investigating the role of periprosthetic fibroblasts (PPFs) in inflammatory osteoclastogenesis reveal contrary results, partly showing an osteoprotective function of fibroblasts and high OPG expression in monolayer. These data disagree with molecular analyses of original periosteolytic tissues. In order to find a more reliable model, PPFs were co-cultivated with peripheral blood mononuclear cells (PBMCs) in a transwell system and compared to conventional monolayer cultures. The gene expression of key regulators of osteoclastogenesis (macrophage colony-stimulating factor (MCSF), receptor activator of NF-κB ligand (RANK-L), osteoprotegerin (OPG), and tumor necrosis factor alpha (TNFα)) as well as the ability of bone resorption were analyzed. In monolayer co-cultures, PPFs executed an osteoprotective function with high OPG-expression, low RANK-L/OPG ratios, and a resulting inhibition of osteolysis even in the presence of MCSF and RANK-L. For transwell co-cultures, profound changes in gene expression, with a more than hundredfold decrease of OPG and a significant upregulation of TNFα were observed. In conclusion, we were able to show that a change of culture conditions towards a transwell system resulted in a considerably more osteoclastogenic gene expression profile, being closer to findings in original periosteolytic tissues. This study therefore presents an interesting approach for a more reliable in vitro model to examine the role of fibroblasts in periprosthetic osteoclastogenesis in the future.

Original languageEnglish
Article number2583
Number of pages16
JournalInternational journal of molecular sciences
Volume20
Issue number10
DOIs
Publication statusPublished - 2 May 2019
Externally publishedYes

Keywords

  • fibroblasts
  • osteolysis
  • osteoclastogenesis
  • aseptic implant loosening
  • transwell culture
  • KAPPA-B LIGAND
  • NECROSIS-FACTOR-ALPHA
  • PERIODONTAL-LIGAMENT CELLS
  • TOTAL KNEE ARTHROPLASTY
  • RECEPTOR ACTIVATOR
  • BONE-RESORPTION
  • INDUCE OSTEOCLASTOGENESIS
  • OSTEOPROTEGERIN LIGAND
  • GINGIVAL FIBROBLASTS
  • HIP-ARTHROPLASTY

Cite this

Koehler, M. I., Hartmann, E. S., Schluessel, S., Beck, F., Redeker, J. I., Schmitt, B., Unger, M., van Griensven, M., Summer, B., Fottner, A., & Mayer-Wagner, S. (2019). Impact of Periprosthetic Fibroblast-Like Cells on Osteoclastogenesis in Co-Culture with Peripheral Blood Mononuclear Cells Varies Depending on Culture System. International journal of molecular sciences, 20(10), [2583]. https://doi.org/10.3390/ijms20102583