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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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OC derived from MHCII+CD16+ and MHCII+CD16- cells of HC and PsA patients have distinct phenotypes. Peripheral blood mononuclear cells (PBMC) isolated from (a and b) psoriatic arthritis (PsA) and (c and d) healthy controls (HC) and were sterile sorted into (a and c) MHCII+CD16+ and (b and d) MHCII+CD16- populations. Sorted cells were cultured in the presence of receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) for eight days, and tartrate-resistant acid phosphatase stained for osteoclast (OC) quantification. Arrows indicate mature OC. The details of differences in OC generation potential and numbers of nuclei from these sorted subsets are summarized in Table 4.
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Figure 5: OC derived from MHCII+CD16+ and MHCII+CD16- cells of HC and PsA patients have distinct phenotypes. Peripheral blood mononuclear cells (PBMC) isolated from (a and b) psoriatic arthritis (PsA) and (c and d) healthy controls (HC) and were sterile sorted into (a and c) MHCII+CD16+ and (b and d) MHCII+CD16- populations. Sorted cells were cultured in the presence of receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) for eight days, and tartrate-resistant acid phosphatase stained for osteoclast (OC) quantification. Arrows indicate mature OC. The details of differences in OC generation potential and numbers of nuclei from these sorted subsets are summarized in Table 4.

Mentions: Morphologic analysis provides additional support for the existence of divergent monocyte subsets with OC differentiation potential in PsA subjects compared with controls (Figure 5). OC derived from CD16+ monocytes in PsA subjects (Figure 5(a)) and CD16- cells cultured from HC (Figure 5(d)) were similar in regard to cell size and nuclear number. In contrast, OC derived from CD16- monocytes in PsA (Figure 5(b)) and CD16+ monocytes in HC (Figure 5(c)) displayed similar morphologic features. Furthermore, OCP from PsA subjects were larger and had more nuclei than those observed in controls. The relative cell diameter of OC derived from CD16+ cells in PsA was five times greater than the diameter observed in OC cultured from control CD16- cells (compare Figure 5(a) with 5(c)). The average number of nuclei per OC in PsA subjects was 12 ± 1.1 compared with 5 ± 0.2 in HC. The morphological differences in these cell subsets are summarized in Table 4.


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)

OC derived from MHCII+CD16+ and MHCII+CD16- cells of HC and PsA patients have distinct phenotypes. Peripheral blood mononuclear cells (PBMC) isolated from (a and b) psoriatic arthritis (PsA) and (c and d) healthy controls (HC) and were sterile sorted into (a and c) MHCII+CD16+ and (b and d) MHCII+CD16- populations. Sorted cells were cultured in the presence of receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) for eight days, and tartrate-resistant acid phosphatase stained for osteoclast (OC) quantification. Arrows indicate mature OC. The details of differences in OC generation potential and numbers of nuclei from these sorted subsets are summarized in Table 4.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

Figure 5: OC derived from MHCII+CD16+ and MHCII+CD16- cells of HC and PsA patients have distinct phenotypes. Peripheral blood mononuclear cells (PBMC) isolated from (a and b) psoriatic arthritis (PsA) and (c and d) healthy controls (HC) and were sterile sorted into (a and c) MHCII+CD16+ and (b and d) MHCII+CD16- populations. Sorted cells were cultured in the presence of receptor activator of nuclear factor kappa-B ligand (RANKL) and macrophage colony-stimulating factor (M-CSF) for eight days, and tartrate-resistant acid phosphatase stained for osteoclast (OC) quantification. Arrows indicate mature OC. The details of differences in OC generation potential and numbers of nuclei from these sorted subsets are summarized in Table 4.
Mentions: Morphologic analysis provides additional support for the existence of divergent monocyte subsets with OC differentiation potential in PsA subjects compared with controls (Figure 5). OC derived from CD16+ monocytes in PsA subjects (Figure 5(a)) and CD16- cells cultured from HC (Figure 5(d)) were similar in regard to cell size and nuclear number. In contrast, OC derived from CD16- monocytes in PsA (Figure 5(b)) and CD16+ monocytes in HC (Figure 5(c)) displayed similar morphologic features. Furthermore, OCP from PsA subjects were larger and had more nuclei than those observed in controls. The relative cell diameter of OC derived from CD16+ cells in PsA was five times greater than the diameter observed in OC cultured from control CD16- cells (compare Figure 5(a) with 5(c)). The average number of nuclei per OC in PsA subjects was 12 ± 1.1 compared with 5 ± 0.2 in HC. The morphological differences in these cell subsets are summarized in Table 4.

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