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Analysis of Mitogen-Activated Protein Kinases in Bone and Cartilage of Patients with Rheumatoid Arthritis Treated with Abatacept.

Kanbe K, Oh K, Chiba J, Inoue Y, Taguchi M, Yabuki A - Clin Med Insights Arthritis Musculoskelet Disord (2016)

Bottom Line: A total of 20 patients of bone and cartilage were assessed: 10 abatacept with methotrexate (MTX)-treated RA patients were compared with 10 MTX-treated RA patients (control).The expressions of CD29 known as mechanoreceptor and ERK known as mechanotransduction signal protein in MAP kinases in the bone and cartilage of patients treated with abatacept were significantly different from those of control.These findings suggest that increases in CD29 and ERK in MAP kinases may change the metabolism of bone and cartilage in RA patients treated with abatacept.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopaedic Surgery, Tokyo Women's Medical University, Tokyo, Japan.

ABSTRACT
The aim of this study was to analyze the histological changes related to mitogen-activated protein (MAP) kinases in bone and cartilage treated with abatacept for rheumatoid arthritis (RA). A total of 20 patients of bone and cartilage were assessed: 10 abatacept with methotrexate (MTX)-treated RA patients were compared with 10 MTX-treated RA patients (control). The histology of bone and cartilage was observed by staining with hematoxylin and eosin and analyzed immunohistochemically for the expression of tumor necrosis factor-α, interleukin-6, CD4 (T cell), CD68 (macrophage), receptor activator of nuclear kappa-B ligand, osteoprotegerin, osteopontin, CD29 (β-1 integrin), phospho-p38 MAPK (Tyr180/Tyr182), phospho-p44/42 MAPK (extracellular signal-regulated kinase, ERK1/ERK2), and phosphor-c-Jun N-terminal kinase. The expressions of CD29 known as mechanoreceptor and ERK known as mechanotransduction signal protein in MAP kinases in the bone and cartilage of patients treated with abatacept were significantly different from those of control. These findings suggest that increases in CD29 and ERK in MAP kinases may change the metabolism of bone and cartilage in RA patients treated with abatacept.

No MeSH data available.


Related in: MedlinePlus

HE staining for bone and cartilage with or without abatacept. (A) and (B): bone; (C) and (D): cartilage; (A) and (C): control group (MTX); (B) and (D): abatacept group, (magnification, 200×).
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f1-cmamd-9-2016-051: HE staining for bone and cartilage with or without abatacept. (A) and (B): bone; (C) and (D): cartilage; (A) and (C): control group (MTX); (B) and (D): abatacept group, (magnification, 200×).

Mentions: Cell proliferation was not significantly different in HE staining of the bone and cartilage with abatacept treatment compared to the subjects in the MTX control group (Figs. 1A–1D). The percentages of positive staining cells for the expression of TNF-α, IL-6, CD4, CD68, RANKL, OPG, and OPN in the bone were not significantly different between control and abatacept [mean (SD): 1.3(1.2), 12.5(4.8), 2.8(2.1), 2.1(1.5), 1.4(0.8), 1.8(1.1), and 1.1(0.5) vs. 1.5(2.3), 10.3(3.5), 3.5(1.6), 6.5(2.4), 1.3(0.5), 1.5(1.6), and 1.5(0.4)]. The percentages of cells stained positive for TNF-α, CD4, CD68, RANKL, OPG, and OPN in cartilage were also not significantly different between control and abatacept except for IL-6 [mean (SD): 2.1(1.8), 1.5(2.3), 4.1(3.5), 1.8(1.7), 2.6(2.0), and 2.1(3.5) vs. 2.5(2.2), 2.8(2.7), 5.5(5.4), 1.2(1.1), 3.8(2.8), and 3.4(3.2); 3.5(2.4) vs. 25.1(7.5) for IL-6]. However, for the immunostaining of MAP kinases, there were significant differences in the expression of CD29 and ERK between control and abatacept with regard to bone and cartilage [mean (SD): 1.3(1.2) and 3.4(1.8) vs. 22(8.3) and 32.3(6.5), P = 0.026 and P = 0.014 in bone marrow; 2.8(2.6) and 5.2(4.7) vs. 34(12.1) and 43.1(15.8), P = 0.016 and P < 0.001 in cartilage] (Tables 2 and 3; Figs. 2A, B, E, and F and 3A, B, E, and F). Therefore, the expressions of CD29 known as mechanoreceptor and ERK known as mechanotransduction signal protein in MAP kinases in the bone and cartilage of patients treated with abatacept were significantly different from control. The patterns of JNK and p38 MAPK were expressed to almost no extent in bone and cartilage in both groups [mean (SD): 2.8(1.1) and 1.1(0.9) vs. 3.5(1.6) and 1.5(1.4) in bone marrow; 4.9(3.1) and 3.2(2.5) vs. 6.5(5.3) and 4.7(4.1) in cartilage] (Tables 2 and 3; Figs. 2C, D, G, and H and 3C, D, G, and H).


Analysis of Mitogen-Activated Protein Kinases in Bone and Cartilage of Patients with Rheumatoid Arthritis Treated with Abatacept.

Kanbe K, Oh K, Chiba J, Inoue Y, Taguchi M, Yabuki A - Clin Med Insights Arthritis Musculoskelet Disord (2016)

HE staining for bone and cartilage with or without abatacept. (A) and (B): bone; (C) and (D): cartilage; (A) and (C): control group (MTX); (B) and (D): abatacept group, (magnification, 200×).
© Copyright Policy - open-access
Related In: Results  -  Collection

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f1-cmamd-9-2016-051: HE staining for bone and cartilage with or without abatacept. (A) and (B): bone; (C) and (D): cartilage; (A) and (C): control group (MTX); (B) and (D): abatacept group, (magnification, 200×).
Mentions: Cell proliferation was not significantly different in HE staining of the bone and cartilage with abatacept treatment compared to the subjects in the MTX control group (Figs. 1A–1D). The percentages of positive staining cells for the expression of TNF-α, IL-6, CD4, CD68, RANKL, OPG, and OPN in the bone were not significantly different between control and abatacept [mean (SD): 1.3(1.2), 12.5(4.8), 2.8(2.1), 2.1(1.5), 1.4(0.8), 1.8(1.1), and 1.1(0.5) vs. 1.5(2.3), 10.3(3.5), 3.5(1.6), 6.5(2.4), 1.3(0.5), 1.5(1.6), and 1.5(0.4)]. The percentages of cells stained positive for TNF-α, CD4, CD68, RANKL, OPG, and OPN in cartilage were also not significantly different between control and abatacept except for IL-6 [mean (SD): 2.1(1.8), 1.5(2.3), 4.1(3.5), 1.8(1.7), 2.6(2.0), and 2.1(3.5) vs. 2.5(2.2), 2.8(2.7), 5.5(5.4), 1.2(1.1), 3.8(2.8), and 3.4(3.2); 3.5(2.4) vs. 25.1(7.5) for IL-6]. However, for the immunostaining of MAP kinases, there were significant differences in the expression of CD29 and ERK between control and abatacept with regard to bone and cartilage [mean (SD): 1.3(1.2) and 3.4(1.8) vs. 22(8.3) and 32.3(6.5), P = 0.026 and P = 0.014 in bone marrow; 2.8(2.6) and 5.2(4.7) vs. 34(12.1) and 43.1(15.8), P = 0.016 and P < 0.001 in cartilage] (Tables 2 and 3; Figs. 2A, B, E, and F and 3A, B, E, and F). Therefore, the expressions of CD29 known as mechanoreceptor and ERK known as mechanotransduction signal protein in MAP kinases in the bone and cartilage of patients treated with abatacept were significantly different from control. The patterns of JNK and p38 MAPK were expressed to almost no extent in bone and cartilage in both groups [mean (SD): 2.8(1.1) and 1.1(0.9) vs. 3.5(1.6) and 1.5(1.4) in bone marrow; 4.9(3.1) and 3.2(2.5) vs. 6.5(5.3) and 4.7(4.1) in cartilage] (Tables 2 and 3; Figs. 2C, D, G, and H and 3C, D, G, and H).

Bottom Line: A total of 20 patients of bone and cartilage were assessed: 10 abatacept with methotrexate (MTX)-treated RA patients were compared with 10 MTX-treated RA patients (control).The expressions of CD29 known as mechanoreceptor and ERK known as mechanotransduction signal protein in MAP kinases in the bone and cartilage of patients treated with abatacept were significantly different from those of control.These findings suggest that increases in CD29 and ERK in MAP kinases may change the metabolism of bone and cartilage in RA patients treated with abatacept.

View Article: PubMed Central - PubMed

Affiliation: Department of Orthopaedic Surgery, Tokyo Women's Medical University, Tokyo, Japan.

ABSTRACT
The aim of this study was to analyze the histological changes related to mitogen-activated protein (MAP) kinases in bone and cartilage treated with abatacept for rheumatoid arthritis (RA). A total of 20 patients of bone and cartilage were assessed: 10 abatacept with methotrexate (MTX)-treated RA patients were compared with 10 MTX-treated RA patients (control). The histology of bone and cartilage was observed by staining with hematoxylin and eosin and analyzed immunohistochemically for the expression of tumor necrosis factor-α, interleukin-6, CD4 (T cell), CD68 (macrophage), receptor activator of nuclear kappa-B ligand, osteoprotegerin, osteopontin, CD29 (β-1 integrin), phospho-p38 MAPK (Tyr180/Tyr182), phospho-p44/42 MAPK (extracellular signal-regulated kinase, ERK1/ERK2), and phosphor-c-Jun N-terminal kinase. The expressions of CD29 known as mechanoreceptor and ERK known as mechanotransduction signal protein in MAP kinases in the bone and cartilage of patients treated with abatacept were significantly different from those of control. These findings suggest that increases in CD29 and ERK in MAP kinases may change the metabolism of bone and cartilage in RA patients treated with abatacept.

No MeSH data available.


Related in: MedlinePlus