title: The Foreign Body Giant Cell Cannot Resorb Bone, But Dissolves Hydroxyapatite Like Osteoclasts.
abstract: Foreign body multinucleated giant cells (FBGCs) and osteoclasts share several characteristics, like a common myeloid precursor cell, multinuclearity, expression of tartrate-resistant acid phosphatase (TRAcP) and dendritic cell-specific transmembrane protein (DC-STAMP). However, there is an important difference: osteoclasts form and reside in the vicinity of bone, while FBGCs form only under pathological conditions or at the surface of foreign materials, like medical implants. Despite similarities, an important distinction between these cell types is that osteoclasts can resorb bone, but it is unknown whether FBGCs are capable of such an activity. To investigate this, we differentiated FBGCs and osteoclasts in vitro from their common CD14+ monocyte precursor cells, using different sets of cytokines. Both cell types were cultured on bovine bone slices and analyzed for typical osteoclast features, such as bone resorption, presence of actin rings, formation of a ruffled border, and characteristic gene expression over time. Additionally, both cell types were cultured on a biomimetic hydroxyapatite coating to discriminate between bone resorption and mineral dissolution independent of organic matrix proteolysis. Both cell types differentiated into multinucleated cells on bone, but FBGCs were larger and had a higher number of nuclei compared to osteoclasts. FBGCs were not able to resorb bone, yet they were able to dissolve the mineral fraction of bone at the surface. Remarkably, FBGCs also expressed actin rings, podosome belts and sealing zones--cytoskeletal organization that is considered to be osteoclast-specific. However, they did not form a ruffled border. At the gene expression level, FBGCs and osteoclasts expressed similar levels of mRNAs that are associated with the dissolution of mineral (e.g., anion exchange protein 2 (AE2), carbonic anhydrase 2 (CAII), chloride channel 7 (CIC7), and vacuolar-type H+-ATPase (v-ATPase)), in contrast the matrix degrading enzyme cathepsin K, which was hardly expressed by FBGCs. Functionally, the latter cells were able to dissolve a biomimetic hydroxyapatite coating in vitro, which was blocked by inhibiting v-ATPase enzyme activity. These results show that FBGCs have the capacity to dissolve the mineral phase of bone, similar to osteoclasts. However, they are not able to digest the matrix fraction of bone, likely due to the lack of a ruffled border and cathepsin K.
authors.affiliation: Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), MOVE Research Institute, University of Amsterdam and VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Bas
authors.initials: B
authors.lastname: ten Harkel
authors.affiliation: Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), MOVE Research Institute, University of Amsterdam and VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Ton
authors.initials: T
authors.lastname: Schoenmaker
authors.affiliation: Department of Cell Biology and Histology, Center for Advanced Microscopy, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
authors.forename: Daisy I
authors.initials: DI
authors.lastname: Picavet
authors.affiliation: MIRA Institute for Biomedical Technology and Technical Medicine, University of Twente, Enschede, The Netherlands; Xpand Biotechnology BV, Bilthoven, The Netherlands.
authors.forename: Noel L
authors.initials: NL
authors.lastname: Davison
authors.affiliation: Department of Periodontology, Academic Centre for Dentistry Amsterdam (ACTA), MOVE Research Institute, University of Amsterdam and VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Teun J
authors.initials: TJ
authors.lastname: de Vries
authors.affiliation: Department of Oral Cell Biology, Academic Centre for Dentistry Amsterdam (ACTA), MOVE Research Institute, University of Amsterdam and VU University Amsterdam, Amsterdam, The Netherlands.
authors.forename: Vincent
authors.initials: V
authors.lastname: Everts
mesh_terms: D000818:Animals; D001862:Bone Resorption / Q000378:metabolism / Q000473:pathology*; D002417:Cattle; D002454:Cell Differentiation; D017886:Durapatite / Q000378:metabolism*; D015743:Giant Cells, Foreign-Body / Q000166:cytology* / Q000378:metabolism; D007124:Immunoenzyme Techniques; D046529:Microscopy, Electron, Transmission; D009000:Monocytes / Q000166:cytology* / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology* / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D017886:Durapatite