Fibroblast-like cells change gene expression of bone remodelling markers in transwell cultures

Eur J Med Res. 2020 Oct 29;25(1):52. doi: 10.1186/s40001-020-00453-y.

Abstract

Introduction: Periprosthetic fibroblast-like cells (PPFs) play an important role in aseptic loosening of arthroplasties. Various studies have examined PPF behavior in monolayer culture systems. However, the periprosthetic tissue is a three-dimensional (3D) mesh, which allows the cells to interact in a multidirectional way. The expression of bone remodeling markers of fibroblast-like cells in a multilayer environment changes significantly versus monolayer cultures without the addition of particles or cytokine stimulation. Gene expression of bone remodeling markers was therefore compared in fibroblast-like cells from different origins and dermal fibroblasts under transwell culture conditions versus monolayer cultures.

Methods: PPFs from periprosthetic tissues (n = 12), osteoarthritic (OA) synovial fibroblast-like cells (SFs) (n = 6), and dermal fibroblasts (DFs) were cultured in monolayer (density 5.5 × 103/cm2) or multilayer cultures (density 8.5 × 105/cm2) for 10 or 21 days. Cultures were examined via histology, TRAP staining, immunohistochemistry (anti-S100a4), and quantitative real-time PCR.

Results: Fibroblast-like cells (PPFs/SFs) and dermal fibroblasts significantly increased the expression of RANKL and significantly decreased the expression of ALP, COL1A1, and OPG in multilayer cultures. PPFs and SFs in multilayer cultures further showed a higher expression of cathepsin K, MMP-13, and TNF-α. In multilayer PPF cultures, the mRNA level of TRAP was also found to be significantly increased.

Conclusion: The multilayer cultures are able to induce significant expression changes in fibroblast-like cells depending on the nature of cellular origin without the addition of any further stimulus. This system might be a useful tool to get more in vivo like results regarding fibroblast-like cell cultures.

Keywords: Aseptic loosening; Bone remodeling; Fibroblast-like cells; Implant material; Transwell culture.

MeSH terms

  • Aged
  • Aged, 80 and over
  • Biomarkers / metabolism*
  • Bone Remodeling / genetics*
  • Cathepsin K / genetics
  • Cathepsin K / metabolism
  • Cell Culture Techniques / instrumentation
  • Cell Culture Techniques / methods*
  • Cells, Cultured
  • Collagen Type I / genetics
  • Collagen Type I / metabolism
  • Collagen Type I, alpha 1 Chain
  • Female
  • Fibroblasts / cytology
  • Fibroblasts / metabolism*
  • Gene Expression*
  • Humans
  • Male
  • Matrix Metalloproteinase 13 / genetics
  • Matrix Metalloproteinase 13 / metabolism
  • Middle Aged
  • Osteoarthritis / pathology
  • Osteoprotegerin / genetics
  • Osteoprotegerin / metabolism
  • RANK Ligand / genetics
  • RANK Ligand / metabolism
  • Synovial Membrane / cytology
  • Tumor Necrosis Factor-alpha / genetics
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Biomarkers
  • Collagen Type I
  • Collagen Type I, alpha 1 Chain
  • Osteoprotegerin
  • RANK Ligand
  • TNFRSF11B protein, human
  • Tumor Necrosis Factor-alpha
  • Cathepsin K
  • Matrix Metalloproteinase 13