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Differentiation of monocytes into multinucleated giant bone-resorbing cells: two-step differentiation induced by nurse-like cells and cytokines.

Toyosaki-Maeda T, Takano H, Tomita T, Tsuruta Y, Maeda-Tanimura M, Shimaoka Y, Takahashi T, Itoh T, Suzuki R, Ochi T - Arthritis Res. (2001)

Bottom Line: The characteristics of these cells are not completely known.These mononuclear cells then differentiated into multinucleated giant bone-resorbing cells after stimulation with IL-3, IL-5, IL-7, and/or granulocyte-macrophage-colony-stimulating factor.TRAP-positive cells with similar characteristics were found in synovial fluid from patients with RA.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopedic Surgery, Osaka University Medical School, Yamada-Oka 2-2, Suita, Osaka 566-0871, Japan.

ABSTRACT
Bone resorption in the joints is the characteristic finding in patients with rheumatoid arthritis (RA). Osteoclast-like cells are present in the synovial tissues and invade the bone of patients with RA. The characteristics of these cells are not completely known. In the work reported here, we generated these cells from peripheral-blood monocytes from healthy individuals. The monocytes were co-cultured with nurse-like cells from synovial tissues of patients with RA (RA-NLCs). Within 5 weeks of culture, the monocytes were activated and differentiated into mononuclear cells positive for CD14 and tartrate-resistant acid phosphatase (TRAP). These mononuclear cells then differentiated into multinucleated giant bone-resorbing cells after stimulation with IL-3, IL-5, IL-7, and/or granulocyte-macrophage-colony-stimulating factor. TRAP-positive cells with similar characteristics were found in synovial fluid from patients with RA. These results indicate that multinucleated giant bone-resorbing cells are generated from monocytes in two steps: first, RA-NLCs induce monocytes to differentiate into TRAP-positive mononuclear cells, which are then induced by cytokines to differentiate into multinucleated giant bone-resorbing cells.

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Immunohistochemical staining of multinucleated giant bone-resorbing cells. The cells were stained green for (a) carbonic anhydrase II and (b) vitronectin receptor. The cells were also positive for (c) actin, which showed red, ring-form staining. (d)In situ detection of calcitonin receptor using 125I-human calcitonin. Black grains mark the cells expressing calcitonin receptor. The multinucleated giant bone-resorbing cells were incubated with 125I-human calcitonin for 1 h. The cells were washed, fixed, and dried as described in the Supplementary materials and methods section. Air-dried slides were exposed at 4ºC for 10 days. Scale lines = 100 μm.
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Figure 3: Immunohistochemical staining of multinucleated giant bone-resorbing cells. The cells were stained green for (a) carbonic anhydrase II and (b) vitronectin receptor. The cells were also positive for (c) actin, which showed red, ring-form staining. (d)In situ detection of calcitonin receptor using 125I-human calcitonin. Black grains mark the cells expressing calcitonin receptor. The multinucleated giant bone-resorbing cells were incubated with 125I-human calcitonin for 1 h. The cells were washed, fixed, and dried as described in the Supplementary materials and methods section. Air-dried slides were exposed at 4ºC for 10 days. Scale lines = 100 μm.

Mentions: The TRAP-positive mononuclear cells, whether induced from monocytes or collected from the synovial fluid of patients with RA, strongly expressed CD11b, CD11c, CD14, CD45, HLA-A, HLA-B, HLA-C, and HLA-DR but did not express CD1a, CD1b, CD2, CD4, CD5, CD16, CD19, CD20, or CD83. These observations suggest that these cells belong to the monocyte/macrophage lineage (Supplementary Table 1). However, the cells did not express CD11a, CD35, or CD68, which are expressed on freshly isolated monocytes from peripheral blood (Supplementary Table 2). The TRAP-positive mononuclear cells had strong phagocytic activity against heat-killed yeast (data not presented). In addition, the cells were positive for carbonic anhydrase II, actin, and vitronectin receptor (Supplementary Fig. 1), and calcitonin receptors were also detected (Supplementary Fig. 1); these four receptors are considered characteristic of osteoclasts [10,23].


Differentiation of monocytes into multinucleated giant bone-resorbing cells: two-step differentiation induced by nurse-like cells and cytokines.

Toyosaki-Maeda T, Takano H, Tomita T, Tsuruta Y, Maeda-Tanimura M, Shimaoka Y, Takahashi T, Itoh T, Suzuki R, Ochi T - Arthritis Res. (2001)

Immunohistochemical staining of multinucleated giant bone-resorbing cells. The cells were stained green for (a) carbonic anhydrase II and (b) vitronectin receptor. The cells were also positive for (c) actin, which showed red, ring-form staining. (d)In situ detection of calcitonin receptor using 125I-human calcitonin. Black grains mark the cells expressing calcitonin receptor. The multinucleated giant bone-resorbing cells were incubated with 125I-human calcitonin for 1 h. The cells were washed, fixed, and dried as described in the Supplementary materials and methods section. Air-dried slides were exposed at 4ºC for 10 days. Scale lines = 100 μm.
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC64843&req=5

Figure 3: Immunohistochemical staining of multinucleated giant bone-resorbing cells. The cells were stained green for (a) carbonic anhydrase II and (b) vitronectin receptor. The cells were also positive for (c) actin, which showed red, ring-form staining. (d)In situ detection of calcitonin receptor using 125I-human calcitonin. Black grains mark the cells expressing calcitonin receptor. The multinucleated giant bone-resorbing cells were incubated with 125I-human calcitonin for 1 h. The cells were washed, fixed, and dried as described in the Supplementary materials and methods section. Air-dried slides were exposed at 4ºC for 10 days. Scale lines = 100 μm.
Mentions: The TRAP-positive mononuclear cells, whether induced from monocytes or collected from the synovial fluid of patients with RA, strongly expressed CD11b, CD11c, CD14, CD45, HLA-A, HLA-B, HLA-C, and HLA-DR but did not express CD1a, CD1b, CD2, CD4, CD5, CD16, CD19, CD20, or CD83. These observations suggest that these cells belong to the monocyte/macrophage lineage (Supplementary Table 1). However, the cells did not express CD11a, CD35, or CD68, which are expressed on freshly isolated monocytes from peripheral blood (Supplementary Table 2). The TRAP-positive mononuclear cells had strong phagocytic activity against heat-killed yeast (data not presented). In addition, the cells were positive for carbonic anhydrase II, actin, and vitronectin receptor (Supplementary Fig. 1), and calcitonin receptors were also detected (Supplementary Fig. 1); these four receptors are considered characteristic of osteoclasts [10,23].

Bottom Line: The characteristics of these cells are not completely known.These mononuclear cells then differentiated into multinucleated giant bone-resorbing cells after stimulation with IL-3, IL-5, IL-7, and/or granulocyte-macrophage-colony-stimulating factor.TRAP-positive cells with similar characteristics were found in synovial fluid from patients with RA.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopedic Surgery, Osaka University Medical School, Yamada-Oka 2-2, Suita, Osaka 566-0871, Japan.

ABSTRACT
Bone resorption in the joints is the characteristic finding in patients with rheumatoid arthritis (RA). Osteoclast-like cells are present in the synovial tissues and invade the bone of patients with RA. The characteristics of these cells are not completely known. In the work reported here, we generated these cells from peripheral-blood monocytes from healthy individuals. The monocytes were co-cultured with nurse-like cells from synovial tissues of patients with RA (RA-NLCs). Within 5 weeks of culture, the monocytes were activated and differentiated into mononuclear cells positive for CD14 and tartrate-resistant acid phosphatase (TRAP). These mononuclear cells then differentiated into multinucleated giant bone-resorbing cells after stimulation with IL-3, IL-5, IL-7, and/or granulocyte-macrophage-colony-stimulating factor. TRAP-positive cells with similar characteristics were found in synovial fluid from patients with RA. These results indicate that multinucleated giant bone-resorbing cells are generated from monocytes in two steps: first, RA-NLCs induce monocytes to differentiate into TRAP-positive mononuclear cells, which are then induced by cytokines to differentiate into multinucleated giant bone-resorbing cells.

Show MeSH
Related in: MedlinePlus