T helper cells promote disease progression of osteoarthritis by inducing macrophage inflammatory protein-1γ

P. C. Shen, Chao-Liang Wu, I. M. Jou, C. H. Lee, H. Y. Juan, P. J. Lee, Shun-hua Chen, J. L. Hsieh

Research output: Contribution to journalArticle

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Abstract

Objective: Immune cells are involved in the pathogenesis of osteoarthritis (OA). We examined the effects of T helper (Th) cells, which induce the expression of macrophage inflammatory protein (MIP-1γ), on the progression of OA. Design: Using anterior cruciate ligament-transection (ACLT), we induced OA in one hind-leg knee joint of B6 mice. The CD4+ T cells from splenocytes and synovium were flow-cytometrically and immunochemically evaluated, respectively. The knee joints were histologically assessed for manifestations of OA. MIP-1γ levels and nuclear factor-κB (NF-κB) in the knee joints were measured using enzyme-linked immunosorbent and immunoblotting assays, respectively; osteoclastogenesis was detected by tartrate-resistant acid phosphatase (TRAP) staining. The inflammatory responses and MIP-1γ expression were examined using immunohistochemistry. Results: The number of CD4+ T cells and the expression of interferon-γ (IFN-γ) increased during OA onset (30 days after ACLT) and then decreased at a later stage of OA (90 days after ACLT). Tissue damage induced by CD4+ T cells was evident at the later stage. The activation of CD4+ T cells induced the expression of MIP-1γ and NF-κB. The expression of MIP-1γ can be detected in synovium which CD4+ T cells were infiltrated. The increased MIP-1γ expression caused an increase in the number of osteoclasts in joints. The regulation of CD4+ T cells was accompanied by increased macrophage infiltration and matrix metalloproteinase (MMP)-9 expression. Histopathological examinations revealed that CD4+ T cell knockout (CD4-/-) mice had less expression of MIP-1γ and slower cartilage degeneration than control mice had. Conclusions: CD4+ T cells were activated during the onset of OA, but cartilage damage was more prominent at a later stage. CD4+ T cells were involved in the pathogenesis of OA: they induced MIP-1γ expression and subsequent osteoclast formation.

Original languageEnglish
Pages (from-to)728-736
Number of pages9
JournalOsteoarthritis and Cartilage
Volume19
Issue number6
DOIs
Publication statusPublished - 2011 Jun 1

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Macrophage Inflammatory Proteins
T-cells
Macrophages
Helper-Inducer T-Lymphocytes
Osteoarthritis
Disease Progression
Proteins
T-Lymphocytes
Anterior Cruciate Ligament
Ligaments
Knee Joint
Synovial Membrane
Cartilage
Osteoclasts
Interferons
Phosphatases
Matrix Metalloproteinase 9
Infiltration
Immunoblotting
Osteogenesis

All Science Journal Classification (ASJC) codes

  • Rheumatology
  • Biomedical Engineering
  • Orthopedics and Sports Medicine

Cite this

Shen, P. C. ; Wu, Chao-Liang ; Jou, I. M. ; Lee, C. H. ; Juan, H. Y. ; Lee, P. J. ; Chen, Shun-hua ; Hsieh, J. L. / T helper cells promote disease progression of osteoarthritis by inducing macrophage inflammatory protein-1γ. In: Osteoarthritis and Cartilage. 2011 ; Vol. 19, No. 6. pp. 728-736.
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abstract = "Objective: Immune cells are involved in the pathogenesis of osteoarthritis (OA). We examined the effects of T helper (Th) cells, which induce the expression of macrophage inflammatory protein (MIP-1γ), on the progression of OA. Design: Using anterior cruciate ligament-transection (ACLT), we induced OA in one hind-leg knee joint of B6 mice. The CD4+ T cells from splenocytes and synovium were flow-cytometrically and immunochemically evaluated, respectively. The knee joints were histologically assessed for manifestations of OA. MIP-1γ levels and nuclear factor-κB (NF-κB) in the knee joints were measured using enzyme-linked immunosorbent and immunoblotting assays, respectively; osteoclastogenesis was detected by tartrate-resistant acid phosphatase (TRAP) staining. The inflammatory responses and MIP-1γ expression were examined using immunohistochemistry. Results: The number of CD4+ T cells and the expression of interferon-γ (IFN-γ) increased during OA onset (30 days after ACLT) and then decreased at a later stage of OA (90 days after ACLT). Tissue damage induced by CD4+ T cells was evident at the later stage. The activation of CD4+ T cells induced the expression of MIP-1γ and NF-κB. The expression of MIP-1γ can be detected in synovium which CD4+ T cells were infiltrated. The increased MIP-1γ expression caused an increase in the number of osteoclasts in joints. The regulation of CD4+ T cells was accompanied by increased macrophage infiltration and matrix metalloproteinase (MMP)-9 expression. Histopathological examinations revealed that CD4+ T cell knockout (CD4-/-) mice had less expression of MIP-1γ and slower cartilage degeneration than control mice had. Conclusions: CD4+ T cells were activated during the onset of OA, but cartilage damage was more prominent at a later stage. CD4+ T cells were involved in the pathogenesis of OA: they induced MIP-1γ expression and subsequent osteoclast formation.",
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T helper cells promote disease progression of osteoarthritis by inducing macrophage inflammatory protein-1γ. / Shen, P. C.; Wu, Chao-Liang; Jou, I. M.; Lee, C. H.; Juan, H. Y.; Lee, P. J.; Chen, Shun-hua; Hsieh, J. L.

In: Osteoarthritis and Cartilage, Vol. 19, No. 6, 01.06.2011, p. 728-736.

Research output: Contribution to journalArticle

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T1 - T helper cells promote disease progression of osteoarthritis by inducing macrophage inflammatory protein-1γ

AU - Shen, P. C.

AU - Wu, Chao-Liang

AU - Jou, I. M.

AU - Lee, C. H.

AU - Juan, H. Y.

AU - Lee, P. J.

AU - Chen, Shun-hua

AU - Hsieh, J. L.

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N2 - Objective: Immune cells are involved in the pathogenesis of osteoarthritis (OA). We examined the effects of T helper (Th) cells, which induce the expression of macrophage inflammatory protein (MIP-1γ), on the progression of OA. Design: Using anterior cruciate ligament-transection (ACLT), we induced OA in one hind-leg knee joint of B6 mice. The CD4+ T cells from splenocytes and synovium were flow-cytometrically and immunochemically evaluated, respectively. The knee joints were histologically assessed for manifestations of OA. MIP-1γ levels and nuclear factor-κB (NF-κB) in the knee joints were measured using enzyme-linked immunosorbent and immunoblotting assays, respectively; osteoclastogenesis was detected by tartrate-resistant acid phosphatase (TRAP) staining. The inflammatory responses and MIP-1γ expression were examined using immunohistochemistry. Results: The number of CD4+ T cells and the expression of interferon-γ (IFN-γ) increased during OA onset (30 days after ACLT) and then decreased at a later stage of OA (90 days after ACLT). Tissue damage induced by CD4+ T cells was evident at the later stage. The activation of CD4+ T cells induced the expression of MIP-1γ and NF-κB. The expression of MIP-1γ can be detected in synovium which CD4+ T cells were infiltrated. The increased MIP-1γ expression caused an increase in the number of osteoclasts in joints. The regulation of CD4+ T cells was accompanied by increased macrophage infiltration and matrix metalloproteinase (MMP)-9 expression. Histopathological examinations revealed that CD4+ T cell knockout (CD4-/-) mice had less expression of MIP-1γ and slower cartilage degeneration than control mice had. Conclusions: CD4+ T cells were activated during the onset of OA, but cartilage damage was more prominent at a later stage. CD4+ T cells were involved in the pathogenesis of OA: they induced MIP-1γ expression and subsequent osteoclast formation.

AB - Objective: Immune cells are involved in the pathogenesis of osteoarthritis (OA). We examined the effects of T helper (Th) cells, which induce the expression of macrophage inflammatory protein (MIP-1γ), on the progression of OA. Design: Using anterior cruciate ligament-transection (ACLT), we induced OA in one hind-leg knee joint of B6 mice. The CD4+ T cells from splenocytes and synovium were flow-cytometrically and immunochemically evaluated, respectively. The knee joints were histologically assessed for manifestations of OA. MIP-1γ levels and nuclear factor-κB (NF-κB) in the knee joints were measured using enzyme-linked immunosorbent and immunoblotting assays, respectively; osteoclastogenesis was detected by tartrate-resistant acid phosphatase (TRAP) staining. The inflammatory responses and MIP-1γ expression were examined using immunohistochemistry. Results: The number of CD4+ T cells and the expression of interferon-γ (IFN-γ) increased during OA onset (30 days after ACLT) and then decreased at a later stage of OA (90 days after ACLT). Tissue damage induced by CD4+ T cells was evident at the later stage. The activation of CD4+ T cells induced the expression of MIP-1γ and NF-κB. The expression of MIP-1γ can be detected in synovium which CD4+ T cells were infiltrated. The increased MIP-1γ expression caused an increase in the number of osteoclasts in joints. The regulation of CD4+ T cells was accompanied by increased macrophage infiltration and matrix metalloproteinase (MMP)-9 expression. Histopathological examinations revealed that CD4+ T cell knockout (CD4-/-) mice had less expression of MIP-1γ and slower cartilage degeneration than control mice had. Conclusions: CD4+ T cells were activated during the onset of OA, but cartilage damage was more prominent at a later stage. CD4+ T cells were involved in the pathogenesis of OA: they induced MIP-1γ expression and subsequent osteoclast formation.

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