Co-culture model using human osteoblasts and osteoclasts on bone discs for in situ monitoring of surface remodeling
(English)In: Biomatter, ISSN 2159-2535Article in journal (Other academic) Submitted
Osteoporosis is marked by accelerated bone resorption than bone formation and is currently treated with suboptimal drugs associated with severe off-target effects. More robust in vitro models are needed to investigate the precise pharmacokinetic effects of new drug formulations on bone cells in coculture conditions. This would promote targeted drug development and could reduce the number of animals needed in pre-clinical trials. However, existing coculture models do not address the effect of soluble factors released from cells in coculture. To address this challenge, we developed a two-sided co-culture model comprising human osteoclasts and osteoblasts on opposite sides of a thin decellurized bone chip. Essential cellular functions such as resorption by osteoclasts and mineralization by osteoblasts were not disrupted in the two-sided co-culture, even though the bone chip physically separated the two cell types. In this model, we freshly quantified resorption pits and mineralization on opposite sides of the same material through microscopy assisted image analysis and histological staining, respectively. Mineralization by osteoblasts was assessed with alizarin red and showed downregulation by 25% in the presence of osteoclasts (relative to osteoblasts alone) on the bone chip. The drug Pamidronate reduced the osteoclast population by 10% without affecting the number of osteoblasts. Thus, this co-culture model significantly simplifies allows in-situ monitoring of the effect of soluble bone signaling factors and anti-osteoporotic drugs.
Place, publisher, year, edition, pages
Taylor & Francis Group.
Research subject Chemistry with specialization in Polymer Chemistry; Chemistry with specialization in Materials Chemistry; Biology with specialization in Molecular Biology
IdentifiersURN: urn:nbn:se:uu:diva-259080OAI: oai:DiVA.org:uu-259080DiVA: diva2:843136
FunderEU, FP7, Seventh Framework Programme, 238551Swedish Research Council, 2014-6099