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The Foreign Body Giant Cell Cannot Resorb Bone, But Dissolves Hydroxyapatite Like Osteoclasts.

ten Harkel B, Schoenmaker T, Picavet DI, Davison NL, de Vries TJ, Everts V - PLoS ONE (2015)

Bottom Line: 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.These results show that FBGCs have the capacity to dissolve the mineral phase of bone, similar to osteoclasts.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus

Resorption activity of osteoclasts and FBGCs on biomimetic hydroxyapatite coatings after concanamycin A treatment.Cells were cultured for 25 days and stained with acridine orange to visualize sites with low pH. Osteoclasts (left column) and FBGCs (right column) stained positive for acridine orange on both bone (a, f; white dashed circles) and tissue culture plastic (b, g; black dashed circles). After incubation with concanamycin A, acridine orange-positive vacuoles were hardly detected (c, h); moreover, dissolution of hydroxyapatite was blocked (d, I; osteoclasts and FBGCs are visible in black dashed circles) compared to control cells cultured without concamycin A (e, j). Cells were stained for TRAcP and DAPI. Scale bar = 100 μm.
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pone.0139564.g007: Resorption activity of osteoclasts and FBGCs on biomimetic hydroxyapatite coatings after concanamycin A treatment.Cells were cultured for 25 days and stained with acridine orange to visualize sites with low pH. Osteoclasts (left column) and FBGCs (right column) stained positive for acridine orange on both bone (a, f; white dashed circles) and tissue culture plastic (b, g; black dashed circles). After incubation with concanamycin A, acridine orange-positive vacuoles were hardly detected (c, h); moreover, dissolution of hydroxyapatite was blocked (d, I; osteoclasts and FBGCs are visible in black dashed circles) compared to control cells cultured without concamycin A (e, j). Cells were stained for TRAcP and DAPI. Scale bar = 100 μm.

Mentions: Acidic lysosomal compartments were visualized with acridine orange in both cell types on bone (Fig 7a and 7f) and on plastic (Fig 7b and 7g). Blocking of v-ATPase with ConcA resulted in an almost complete abrogation of acridine orange staining (Fig 7c and 7h). We analyzed this on plastic because it was not possible to visualize the cells on bone due to the lack of staining of acridine orange in the presence of ConcA.


The Foreign Body Giant Cell Cannot Resorb Bone, But Dissolves Hydroxyapatite Like Osteoclasts.

ten Harkel B, Schoenmaker T, Picavet DI, Davison NL, de Vries TJ, Everts V - PLoS ONE (2015)

Resorption activity of osteoclasts and FBGCs on biomimetic hydroxyapatite coatings after concanamycin A treatment.Cells were cultured for 25 days and stained with acridine orange to visualize sites with low pH. Osteoclasts (left column) and FBGCs (right column) stained positive for acridine orange on both bone (a, f; white dashed circles) and tissue culture plastic (b, g; black dashed circles). After incubation with concanamycin A, acridine orange-positive vacuoles were hardly detected (c, h); moreover, dissolution of hydroxyapatite was blocked (d, I; osteoclasts and FBGCs are visible in black dashed circles) compared to control cells cultured without concamycin A (e, j). Cells were stained for TRAcP and DAPI. Scale bar = 100 μm.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4591016&req=5

pone.0139564.g007: Resorption activity of osteoclasts and FBGCs on biomimetic hydroxyapatite coatings after concanamycin A treatment.Cells were cultured for 25 days and stained with acridine orange to visualize sites with low pH. Osteoclasts (left column) and FBGCs (right column) stained positive for acridine orange on both bone (a, f; white dashed circles) and tissue culture plastic (b, g; black dashed circles). After incubation with concanamycin A, acridine orange-positive vacuoles were hardly detected (c, h); moreover, dissolution of hydroxyapatite was blocked (d, I; osteoclasts and FBGCs are visible in black dashed circles) compared to control cells cultured without concamycin A (e, j). Cells were stained for TRAcP and DAPI. Scale bar = 100 μm.
Mentions: Acidic lysosomal compartments were visualized with acridine orange in both cell types on bone (Fig 7a and 7f) and on plastic (Fig 7b and 7g). Blocking of v-ATPase with ConcA resulted in an almost complete abrogation of acridine orange staining (Fig 7c and 7h). We analyzed this on plastic because it was not possible to visualize the cells on bone due to the lack of staining of acridine orange in the presence of ConcA.

Bottom Line: 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.These results show that FBGCs have the capacity to dissolve the mineral phase of bone, similar to osteoclasts.

View Article: PubMed Central - PubMed

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.

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.

No MeSH data available.


Related in: MedlinePlus