A supplement-free osteoclast-osteoblast co-culture for pre-clinical application

J Cell Physiol. 2018 Jun;233(6):4391-4400. doi: 10.1002/jcp.26076. Epub 2017 Aug 23.


There is increasing demand for efficient and physiological in vitro cell culture systems suitable for testing new pharmaceutical drugs or for evaluating materials for tissue regeneration. In particular, co-cultures of two or more tissue-relevant cell types have the advantage to study the response of cells on diverse parameters in a more natural environment with respect to physiological complexity. We developed a direct bone cell co-culture system using human peripheral blood monocytes (hPBMC) and human bone marrow stromal cells (hBMSC) as osteoclast/osteoblast precursor cells, respectively, strictly avoiding external supplements for the induction of differentiation. The sophisticated direct hPBMC/hBMSC co-culture was characterized focusing on osteoclast function and was compared with two indirect approaches. Only in the direct co-culture, hPBMC were triggered by hBMSC into osteoclastogenesis and became active resorbing osteoclasts. Bisphosphonates and sulfated glycosaminoglycans were used to examine the suitability of the co-culture system for evaluating the influence of certain effectors on bone healing and bone regeneration and the contribution of each cell type thereby. The results show that the investigated substances had more pronounced effects on both osteoblasts and osteoclasts in the co-culture system than in respective monocultures.

Keywords: bisphosphonates; bone marrow stromal cells; co-culture; glycosaminoglycans; osteoblasts; osteoclasts; peripheral blood mononuclear cells.

Publication types

  • Comparative Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Biomarkers / metabolism
  • Bone Remodeling
  • Carrier Proteins / metabolism
  • Cell Communication
  • Cell Differentiation
  • Cells, Cultured
  • Coculture Techniques
  • Diphosphonates / pharmacology
  • Glycosaminoglycans / pharmacology
  • Humans
  • Leukocytes, Mononuclear / physiology*
  • Mesenchymal Stem Cells / physiology*
  • Osteoblasts / drug effects
  • Osteoblasts / physiology*
  • Osteoclasts / drug effects
  • Osteoclasts / physiology*
  • Osteogenesis
  • Phenotype
  • Tartrate-Resistant Acid Phosphatase / metabolism


  • Biomarkers
  • Carrier Proteins
  • Diphosphonates
  • Glycosaminoglycans
  • ALPL protein, human
  • Tartrate-Resistant Acid Phosphatase