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CD16 (FcRgammaIII) as a potential marker of osteoclast precursors in psoriatic arthritis.

Chiu YG, Shao T, Feng C, Mensah KA, Thullen M, Schwarz EM, Ritchlin CT - Arthritis Res. Ther. (2010)

Bottom Line: Exposure of cells to OC-promoting, but not DC-promoting media, was associated with CD16 up-regulation.An increased frequency of circulating CD14+CD16+ cells was noted in PsA compared to controls, and intermediate levels of CD16 may suggest a transitional state of OCP during osteoclastogenesis.Collectively, our data suggest that CD16 has the potential to serve as an OCP marker in inflammatory arthritis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Allergy/Immunology & Rheumatology Unit, University of Rochester Medical School, 601 Elmwood Avenue, Rochester, NY 14642, USA. grace_chiu@urmc.rochester.edu

ABSTRACT

Introduction: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis characterized by bone erosion mediated by osteoclasts (OC). Our previous studies showed an elevated frequency of OC precursors (OCP) in PsA patients. Here, we examined if OC arise from CD16-positive monocytes in PsA.

Methods: Peripheral blood mononuclear cells (PBMC) or monocytes were isolated from human peripheral blood and sorted based on CD16 expression. Sorted cells were cultured alone or with bone wafers in the presence of receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Enumeration and bone erosion activity of OC were examined after culture. The effects of tumor necrosis factor-alpha (TNFalpha), OC-promoting (M-CSF plus RANKL), and dendritic cell (DC)-promoting (GM-CSF plus interleukin (IL)-4) cytokines on CD16 surface expression were examined by flow cytometry.

Results: PsA and psoriasis (Ps) subjects had a higher percentage of circulating inflammatory CD14+CD16+ cells than healthy controls (HC). Exposure of cells to OC-promoting, but not DC-promoting media, was associated with CD16 up-regulation. PBMC of Ps and PsA had a higher frequency of cells expressing intermediate levels of CD16. OC were mainly derived from CD16+ cells in PsA. Increased CD16 expression was associated with a higher bone erosion activity in PsA.

Conclusions: An increased frequency of circulating CD14+CD16+ cells was noted in PsA compared to controls, and intermediate levels of CD16 may suggest a transitional state of OCP during osteoclastogenesis. Intriguingly, TNFalpha blocked CD16 expression on a subset of CD14+ monocytes. Collectively, our data suggest that CD16 has the potential to serve as an OCP marker in inflammatory arthritis.

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CD16+ cells have a higher bone resorption activity than CD16int cells. Sterile sorted MHCII+CD16+ and MHCII+CD16int cells were co-cultured with bone slices in the presence of receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) for 14 days. (a) Quantification of bone pits eroded by MHCII+CD16int and MHCII+CD16+ cells. (b) Reconstructed three-dimensional micro-CT images of the bone wafer incubated with MHCII+CD16int [a] and MHCII+CD16+ [b] sorted cells. The data are representative of three independent sorting experiments.
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Figure 8: CD16+ cells have a higher bone resorption activity than CD16int cells. Sterile sorted MHCII+CD16+ and MHCII+CD16int cells were co-cultured with bone slices in the presence of receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) for 14 days. (a) Quantification of bone pits eroded by MHCII+CD16int and MHCII+CD16+ cells. (b) Reconstructed three-dimensional micro-CT images of the bone wafer incubated with MHCII+CD16int [a] and MHCII+CD16+ [b] sorted cells. The data are representative of three independent sorting experiments.

Mentions: In contrast to MHCII+CD16- cells that generated very few TRAP+ cells on the bone wafer (data not shown), both MHCII+CD16int and MHCII+CD16+ cells were able to develop into mature OC (Figure 7(a)-(b)). Figure 7(c)-(d) shows the corresponding bone erosions on the same bone wafers. OC derived from the CD16+ subset generated larger and more numerous pits than those from CD16int cells (Figure 7(c) vs. 7(d)). Next, we used the method published by Zhang and colleagues [26] to quantify bone erosion area. The erosion area of the CD16+ cells was two-fold larger than that eroded by CD16int cells (Figure 8(a)). We also noticed that the depth of erosion pits was also much deeper on the wafers incubated with CD16+ cells (Figure 7(c) vs. 7(d)). To confirm this observation, we used micro-CT technology to obtain three-dimensional images of these wafers (Figure 8(b)). In contrast to a moderate bone erosion observed in CD16int sorted cells (Figure 8(b)-a), a higher number of pits associated with greater depth were found on the wafer incubated with CD16+ sorted cells (Figure 8(b)-b). In conclusion, our results showed that OC derived from CD16+ monocytes had a higher bone erosion activity than CD16int and CD16- monocytes, which supports an association between CD16 surface expression and bone erosion activity.


CD16 (FcRgammaIII) as a potential marker of osteoclast precursors in psoriatic arthritis.

Chiu YG, Shao T, Feng C, Mensah KA, Thullen M, Schwarz EM, Ritchlin CT - Arthritis Res. Ther. (2010)

CD16+ cells have a higher bone resorption activity than CD16int cells. Sterile sorted MHCII+CD16+ and MHCII+CD16int cells were co-cultured with bone slices in the presence of receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) for 14 days. (a) Quantification of bone pits eroded by MHCII+CD16int and MHCII+CD16+ cells. (b) Reconstructed three-dimensional micro-CT images of the bone wafer incubated with MHCII+CD16int [a] and MHCII+CD16+ [b] sorted cells. The data are representative of three independent sorting experiments.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC2875642&req=5

Figure 8: CD16+ cells have a higher bone resorption activity than CD16int cells. Sterile sorted MHCII+CD16+ and MHCII+CD16int cells were co-cultured with bone slices in the presence of receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) for 14 days. (a) Quantification of bone pits eroded by MHCII+CD16int and MHCII+CD16+ cells. (b) Reconstructed three-dimensional micro-CT images of the bone wafer incubated with MHCII+CD16int [a] and MHCII+CD16+ [b] sorted cells. The data are representative of three independent sorting experiments.
Mentions: In contrast to MHCII+CD16- cells that generated very few TRAP+ cells on the bone wafer (data not shown), both MHCII+CD16int and MHCII+CD16+ cells were able to develop into mature OC (Figure 7(a)-(b)). Figure 7(c)-(d) shows the corresponding bone erosions on the same bone wafers. OC derived from the CD16+ subset generated larger and more numerous pits than those from CD16int cells (Figure 7(c) vs. 7(d)). Next, we used the method published by Zhang and colleagues [26] to quantify bone erosion area. The erosion area of the CD16+ cells was two-fold larger than that eroded by CD16int cells (Figure 8(a)). We also noticed that the depth of erosion pits was also much deeper on the wafers incubated with CD16+ cells (Figure 7(c) vs. 7(d)). To confirm this observation, we used micro-CT technology to obtain three-dimensional images of these wafers (Figure 8(b)). In contrast to a moderate bone erosion observed in CD16int sorted cells (Figure 8(b)-a), a higher number of pits associated with greater depth were found on the wafer incubated with CD16+ sorted cells (Figure 8(b)-b). In conclusion, our results showed that OC derived from CD16+ monocytes had a higher bone erosion activity than CD16int and CD16- monocytes, which supports an association between CD16 surface expression and bone erosion activity.

Bottom Line: Exposure of cells to OC-promoting, but not DC-promoting media, was associated with CD16 up-regulation.An increased frequency of circulating CD14+CD16+ cells was noted in PsA compared to controls, and intermediate levels of CD16 may suggest a transitional state of OCP during osteoclastogenesis.Collectively, our data suggest that CD16 has the potential to serve as an OCP marker in inflammatory arthritis.

View Article: PubMed Central - HTML - PubMed

Affiliation: Allergy/Immunology & Rheumatology Unit, University of Rochester Medical School, 601 Elmwood Avenue, Rochester, NY 14642, USA. grace_chiu@urmc.rochester.edu

ABSTRACT

Introduction: Psoriatic arthritis (PsA) is a chronic inflammatory arthritis characterized by bone erosion mediated by osteoclasts (OC). Our previous studies showed an elevated frequency of OC precursors (OCP) in PsA patients. Here, we examined if OC arise from CD16-positive monocytes in PsA.

Methods: Peripheral blood mononuclear cells (PBMC) or monocytes were isolated from human peripheral blood and sorted based on CD16 expression. Sorted cells were cultured alone or with bone wafers in the presence of receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF). Enumeration and bone erosion activity of OC were examined after culture. The effects of tumor necrosis factor-alpha (TNFalpha), OC-promoting (M-CSF plus RANKL), and dendritic cell (DC)-promoting (GM-CSF plus interleukin (IL)-4) cytokines on CD16 surface expression were examined by flow cytometry.

Results: PsA and psoriasis (Ps) subjects had a higher percentage of circulating inflammatory CD14+CD16+ cells than healthy controls (HC). Exposure of cells to OC-promoting, but not DC-promoting media, was associated with CD16 up-regulation. PBMC of Ps and PsA had a higher frequency of cells expressing intermediate levels of CD16. OC were mainly derived from CD16+ cells in PsA. Increased CD16 expression was associated with a higher bone erosion activity in PsA.

Conclusions: An increased frequency of circulating CD14+CD16+ cells was noted in PsA compared to controls, and intermediate levels of CD16 may suggest a transitional state of OCP during osteoclastogenesis. Intriguingly, TNFalpha blocked CD16 expression on a subset of CD14+ monocytes. Collectively, our data suggest that CD16 has the potential to serve as an OCP marker in inflammatory arthritis.

Show MeSH
Related in: MedlinePlus