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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

Osteoclast and FBGC mRNA expression at different time points.Data represent the mean ± S.D. of n = 5 donors. *p<0.05, **p<0.01.
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pone.0139564.g005: Osteoclast and FBGC mRNA expression at different time points.Data represent the mean ± S.D. of n = 5 donors. *p<0.05, **p<0.01.

Mentions: We analyzed the expression of genes related to cell-cell fusion, adhesion, mitochondrial activity, acidification and osteoclast differentiation and function at 18 and 25 days of the culture (Fig 5). DC-STAMP, necessary for fusion of osteoclasts and FBGCs [16] and CD36 (fusion of FBGC) [27], was expressed at both time points (day 18 and day 25). At day 18 no difference was observed between the osteoclasts and the FBGCs, however, at day 25 DC-STAMP and CD36 were significantly upregulated in the FBGCs compared to the osteoclasts (Fig 5a; p<0.01). Beta-3 integrin (attachment), and proto-oncogene tyrosine-protein kinase Src (c-Src) (cytoskeleton reorganization, podosomes) [28] were both expressed but there was no difference between the two cell types (Fig 5b).


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)

Osteoclast and FBGC mRNA expression at different time points.Data represent the mean ± S.D. of n = 5 donors. *p<0.05, **p<0.01.
© Copyright Policy
Related In: Results  -  Collection

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

pone.0139564.g005: Osteoclast and FBGC mRNA expression at different time points.Data represent the mean ± S.D. of n = 5 donors. *p<0.05, **p<0.01.
Mentions: We analyzed the expression of genes related to cell-cell fusion, adhesion, mitochondrial activity, acidification and osteoclast differentiation and function at 18 and 25 days of the culture (Fig 5). DC-STAMP, necessary for fusion of osteoclasts and FBGCs [16] and CD36 (fusion of FBGC) [27], was expressed at both time points (day 18 and day 25). At day 18 no difference was observed between the osteoclasts and the FBGCs, however, at day 25 DC-STAMP and CD36 were significantly upregulated in the FBGCs compared to the osteoclasts (Fig 5a; p<0.01). Beta-3 integrin (attachment), and proto-oncogene tyrosine-protein kinase Src (c-Src) (cytoskeleton reorganization, podosomes) [28] were both expressed but there was no difference between the two cell types (Fig 5b).

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