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CD8+ T cell-induced expression of tissue inhibitor of metalloproteinses-1 exacerbated osteoarthritis.

Hsieh JL, Shiau AL, Lee CH, Yang SJ, Lee BO, Jou IM, Wu CL, Chen SH, Shen PC - Int J Mol Sci (2013)

Bottom Line: We investigated the effects of CD8+ T cells and the expression of tissue inhibitor of metalloproteinases 1 (TIMP-1) on joint pathology.TIMP-1 protein was detected in synovium in which angiogenesis occurred.Furthermore, inhibiting the expression of TIMP-1 in joints could retard the progression of OA.

View Article: PubMed Central - PubMed

Affiliation: Department of Nursing, Chung Hwa University of Medical Technology, Tainan 717, Taiwan. bcshen58@yahoo.com.tw.

ABSTRACT
Despites the fact that T cells are involved in the pathogenesis of osteoarthritis (OA) little is known about the roles of CD8+ T cells in this disease. We investigated the effects of CD8+ T cells and the expression of tissue inhibitor of metalloproteinases 1 (TIMP-1) on joint pathology. Using anterior cruciate ligament-transection (ACLT), OA was induced in mice. The knee joints were histologically assessed for manifestations of OA. The CD8+ T cells from splenocytes and synovium were flow-cytometrically and immunochemically evaluated, respectively. Local expression of TIMP-1, matrix metalloproteinase (MMP)-13, and VEGF were examined. Cartilage degeneration was slower in CD8+ T cell knockout mice than in control mice. CD8+ T cells were activated once OA was initiated and expanded during OA progression. More CD8+ T cells from splenocytes expressed TIMP-1 in ACLT-group mice than in Sham-group mice. The number of TIMP-1-expressing CD8+ T cells in OA mice correlated with the disease severity. TIMP-1 expression in cartilage was co-localized with that of MMP-13 and VEGF. TIMP-1 protein was detected in synovium in which angiogenesis occurred. During the pathogenesis of OA, the expression of TIMP-1, VEGF and MMP-13 accompanying with CD8+ T cells activation were increased. Furthermore, inhibiting the expression of TIMP-1 in joints could retard the progression of OA.

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Immunohistochemical staining for TIMP-1, MMP-13, and VEGF in the joints of mice with OA. Representative immunohistochemical images of the cartilage and synovium are shown (n = 5 per group) (a) Higher TIMP-1, MMP-13, and VEGF expression was seen in the superficial cartilage and in the osteochondral cartilage junctions of ACLT-group mice than in Sham- and CD8−/−/ACLT-group mice 90 days post-surgery (IHC stain; 200× magnification; scale bar = 50 μm). The overlapped locations of three gene expressions are indicated with arrows; and (b) Higher TIMP-1 expression and more abundant angiogenesis were seen in ACLT-group mice synovia than in Sham- and CD8−/−/ACLT-group mice synovia (IHC stain; 200× magnification; scale bar = 50 μm). The overlapped locations of TIMP-1 and vWf expression are indicated with arrows.
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f6-ijms-14-19951: Immunohistochemical staining for TIMP-1, MMP-13, and VEGF in the joints of mice with OA. Representative immunohistochemical images of the cartilage and synovium are shown (n = 5 per group) (a) Higher TIMP-1, MMP-13, and VEGF expression was seen in the superficial cartilage and in the osteochondral cartilage junctions of ACLT-group mice than in Sham- and CD8−/−/ACLT-group mice 90 days post-surgery (IHC stain; 200× magnification; scale bar = 50 μm). The overlapped locations of three gene expressions are indicated with arrows; and (b) Higher TIMP-1 expression and more abundant angiogenesis were seen in ACLT-group mice synovia than in Sham- and CD8−/−/ACLT-group mice synovia (IHC stain; 200× magnification; scale bar = 50 μm). The overlapped locations of TIMP-1 and vWf expression are indicated with arrows.

Mentions: TIMP-1 expression induces MMP-13 expression, which is a key mediator of cartilage degradation in OA. We next examined the MMP-13 expression by IHC in cartilage. Interestingly, the expression of MMP-13 was co-localized with the TIMP-1 expression in the superficial and osteochondral area of cartilage in ACLT-group mice 90 days post-surgery (Figure 6a). The expression of both MMP-13 and TIMP-1 was significantly lower in the CD8−/−/ACLT-group mice than in ACLT-group mice. In addition, VEGF expression was co-localized with TIMP-1 expression in the same areas. Co-localization of TIMP-1 expression and angiogenesis also occurred in the synovia (Figure 6b). TIMP-1 expression was much more abundant in the subsynovial membrane of ACLT-group mice than in that of CD8−/−/ACLT- and Sham-group mice.


CD8+ T cell-induced expression of tissue inhibitor of metalloproteinses-1 exacerbated osteoarthritis.

Hsieh JL, Shiau AL, Lee CH, Yang SJ, Lee BO, Jou IM, Wu CL, Chen SH, Shen PC - Int J Mol Sci (2013)

Immunohistochemical staining for TIMP-1, MMP-13, and VEGF in the joints of mice with OA. Representative immunohistochemical images of the cartilage and synovium are shown (n = 5 per group) (a) Higher TIMP-1, MMP-13, and VEGF expression was seen in the superficial cartilage and in the osteochondral cartilage junctions of ACLT-group mice than in Sham- and CD8−/−/ACLT-group mice 90 days post-surgery (IHC stain; 200× magnification; scale bar = 50 μm). The overlapped locations of three gene expressions are indicated with arrows; and (b) Higher TIMP-1 expression and more abundant angiogenesis were seen in ACLT-group mice synovia than in Sham- and CD8−/−/ACLT-group mice synovia (IHC stain; 200× magnification; scale bar = 50 μm). The overlapped locations of TIMP-1 and vWf expression are indicated with arrows.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3821596&req=5

f6-ijms-14-19951: Immunohistochemical staining for TIMP-1, MMP-13, and VEGF in the joints of mice with OA. Representative immunohistochemical images of the cartilage and synovium are shown (n = 5 per group) (a) Higher TIMP-1, MMP-13, and VEGF expression was seen in the superficial cartilage and in the osteochondral cartilage junctions of ACLT-group mice than in Sham- and CD8−/−/ACLT-group mice 90 days post-surgery (IHC stain; 200× magnification; scale bar = 50 μm). The overlapped locations of three gene expressions are indicated with arrows; and (b) Higher TIMP-1 expression and more abundant angiogenesis were seen in ACLT-group mice synovia than in Sham- and CD8−/−/ACLT-group mice synovia (IHC stain; 200× magnification; scale bar = 50 μm). The overlapped locations of TIMP-1 and vWf expression are indicated with arrows.
Mentions: TIMP-1 expression induces MMP-13 expression, which is a key mediator of cartilage degradation in OA. We next examined the MMP-13 expression by IHC in cartilage. Interestingly, the expression of MMP-13 was co-localized with the TIMP-1 expression in the superficial and osteochondral area of cartilage in ACLT-group mice 90 days post-surgery (Figure 6a). The expression of both MMP-13 and TIMP-1 was significantly lower in the CD8−/−/ACLT-group mice than in ACLT-group mice. In addition, VEGF expression was co-localized with TIMP-1 expression in the same areas. Co-localization of TIMP-1 expression and angiogenesis also occurred in the synovia (Figure 6b). TIMP-1 expression was much more abundant in the subsynovial membrane of ACLT-group mice than in that of CD8−/−/ACLT- and Sham-group mice.

Bottom Line: We investigated the effects of CD8+ T cells and the expression of tissue inhibitor of metalloproteinases 1 (TIMP-1) on joint pathology.TIMP-1 protein was detected in synovium in which angiogenesis occurred.Furthermore, inhibiting the expression of TIMP-1 in joints could retard the progression of OA.

View Article: PubMed Central - PubMed

Affiliation: Department of Nursing, Chung Hwa University of Medical Technology, Tainan 717, Taiwan. bcshen58@yahoo.com.tw.

ABSTRACT
Despites the fact that T cells are involved in the pathogenesis of osteoarthritis (OA) little is known about the roles of CD8+ T cells in this disease. We investigated the effects of CD8+ T cells and the expression of tissue inhibitor of metalloproteinases 1 (TIMP-1) on joint pathology. Using anterior cruciate ligament-transection (ACLT), OA was induced in mice. The knee joints were histologically assessed for manifestations of OA. The CD8+ T cells from splenocytes and synovium were flow-cytometrically and immunochemically evaluated, respectively. Local expression of TIMP-1, matrix metalloproteinase (MMP)-13, and VEGF were examined. Cartilage degeneration was slower in CD8+ T cell knockout mice than in control mice. CD8+ T cells were activated once OA was initiated and expanded during OA progression. More CD8+ T cells from splenocytes expressed TIMP-1 in ACLT-group mice than in Sham-group mice. The number of TIMP-1-expressing CD8+ T cells in OA mice correlated with the disease severity. TIMP-1 expression in cartilage was co-localized with that of MMP-13 and VEGF. TIMP-1 protein was detected in synovium in which angiogenesis occurred. During the pathogenesis of OA, the expression of TIMP-1, VEGF and MMP-13 accompanying with CD8+ T cells activation were increased. Furthermore, inhibiting the expression of TIMP-1 in joints could retard the progression of OA.

Show MeSH
Related in: MedlinePlus