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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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Histological analysis in the knee joints of TIMP-1 neutralization antibody-treated mice (n = 5 per group). Cartilages from the medial femoral condyle are shown. (a) Representative sections of cartilage whose scores were closest to the mean in each group were shown (Safranin-O/fast green stain; 200× magnification, scale bar = 50 μm). The specimens from mice treated with NS and control antibody showed remarkably decreased Safranin-O staining and surface irregularities. The TIMP-1 antibody-treated specimens had an irregular superficial layer of cartilage. The surface layer of cartilage in the Sham group was smooth and showed no significant changes; (b) Histologic examination showed a reduced Mankin’s score in the medial femoral condyles of cartilage from mice treated with TIMP-1 antibody. Each value represents the means ± 95% confidence intervals. Significant difference in scores was observed between control Ab and anti-TIMP-1 Ab groups (p = 0.0011); (c) Representative sections of synovium which scores were the most close to the means in each group were shown (hematoxylin and eosin stain; 200× magnification, scale bar = 50 μm). Synovia in the NS- and control antibody-treated mice showed hyperplasia and hypertrophy of synovial lining cells. The TIMP-1 antibody-treated specimens showed slightly more cell proliferation in the synovial lining and cell infiltration than did the sham-operated specimens; and (d) Histologic examination showed a reduced synovitis score in the synovial tissues of knees from mice treated with TIMP-1 antibody. Each value represents the means ± 95% confidence intervals. Significant difference in scores was observed between control Ab and anti-TIMP-1 Ab groups (p = 0.003).
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f7-ijms-14-19951: Histological analysis in the knee joints of TIMP-1 neutralization antibody-treated mice (n = 5 per group). Cartilages from the medial femoral condyle are shown. (a) Representative sections of cartilage whose scores were closest to the mean in each group were shown (Safranin-O/fast green stain; 200× magnification, scale bar = 50 μm). The specimens from mice treated with NS and control antibody showed remarkably decreased Safranin-O staining and surface irregularities. The TIMP-1 antibody-treated specimens had an irregular superficial layer of cartilage. The surface layer of cartilage in the Sham group was smooth and showed no significant changes; (b) Histologic examination showed a reduced Mankin’s score in the medial femoral condyles of cartilage from mice treated with TIMP-1 antibody. Each value represents the means ± 95% confidence intervals. Significant difference in scores was observed between control Ab and anti-TIMP-1 Ab groups (p = 0.0011); (c) Representative sections of synovium which scores were the most close to the means in each group were shown (hematoxylin and eosin stain; 200× magnification, scale bar = 50 μm). Synovia in the NS- and control antibody-treated mice showed hyperplasia and hypertrophy of synovial lining cells. The TIMP-1 antibody-treated specimens showed slightly more cell proliferation in the synovial lining and cell infiltration than did the sham-operated specimens; and (d) Histologic examination showed a reduced synovitis score in the synovial tissues of knees from mice treated with TIMP-1 antibody. Each value represents the means ± 95% confidence intervals. Significant difference in scores was observed between control Ab and anti-TIMP-1 Ab groups (p = 0.003).

Mentions: To investigate the role of TIMP-1 in the OA, we inhibited the local expression of TIMP-1 when OA was induced. One week after surgery, TIMP-1 neutralization antibody was intraarticularly injected in the OA knees of mice (0.5 mg/kg) once a week for two consecutive weeks. 30 days at sacrifice, cartilages from the mice treated with either NS (normal saline) or an isotype-matched goat IgG antibody (control Ab) showed a remarkably reduction of Safranio-O staining and loss of chondrocytes of surface layer cells (Figure 7a). Nevertheless, in the joints treated with anti-TIMP-1 antibody (anti-TIMP-1 Ab), the severity of lesion was reduced. Slight reduction of Safranin-O staining and some chondrocytes cloning were observed on the superficial layer of cartilage. In the sham-operated knee joints, most of the articular cartilage of the femur had a smooth surface, evenly stained with Safranin-O. The Mankin’s score in the anti-TIMP-1 Ab-treated joints was significantly lower than that in the control Ab-treated ones [5.5 (4.18–6.82) vs. 9.0 (7.54–10.46), p = 0.0011, Figure 7b]. Synovia in NS and control Ab treated-group mice showed hyperplasia and hypertrophy of the lining cells and increased infiltration of inflammatory cells. As compared with the sham-operated group, a slight increase of synovial lining cell proliferation and inflammatory cell infiltration was noted in the anti-TIMP-1 Ab-treated group mice (Figure 7c). The synovitis score in joints treated with anti-TIMP-1 Ab was significantly lower than that treated with control Ab [6.7 (5.02–8.38) vs. 11.1 (8.72–13.48), p = 0.003, Figure 7d]. The intra class coefficients of both scores used for evaluating interobserver’s variation was 0.82, p < 0.001. Taken together, these results indicated that the expression of TIMP-1 increased in the cartilage and synovium of OA mice. Inhibiting its expression could retard the disease progression and attenuate the severity of OA.


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)

Histological analysis in the knee joints of TIMP-1 neutralization antibody-treated mice (n = 5 per group). Cartilages from the medial femoral condyle are shown. (a) Representative sections of cartilage whose scores were closest to the mean in each group were shown (Safranin-O/fast green stain; 200× magnification, scale bar = 50 μm). The specimens from mice treated with NS and control antibody showed remarkably decreased Safranin-O staining and surface irregularities. The TIMP-1 antibody-treated specimens had an irregular superficial layer of cartilage. The surface layer of cartilage in the Sham group was smooth and showed no significant changes; (b) Histologic examination showed a reduced Mankin’s score in the medial femoral condyles of cartilage from mice treated with TIMP-1 antibody. Each value represents the means ± 95% confidence intervals. Significant difference in scores was observed between control Ab and anti-TIMP-1 Ab groups (p = 0.0011); (c) Representative sections of synovium which scores were the most close to the means in each group were shown (hematoxylin and eosin stain; 200× magnification, scale bar = 50 μm). Synovia in the NS- and control antibody-treated mice showed hyperplasia and hypertrophy of synovial lining cells. The TIMP-1 antibody-treated specimens showed slightly more cell proliferation in the synovial lining and cell infiltration than did the sham-operated specimens; and (d) Histologic examination showed a reduced synovitis score in the synovial tissues of knees from mice treated with TIMP-1 antibody. Each value represents the means ± 95% confidence intervals. Significant difference in scores was observed between control Ab and anti-TIMP-1 Ab groups (p = 0.003).
© Copyright Policy - open-access
Related In: Results  -  Collection

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

f7-ijms-14-19951: Histological analysis in the knee joints of TIMP-1 neutralization antibody-treated mice (n = 5 per group). Cartilages from the medial femoral condyle are shown. (a) Representative sections of cartilage whose scores were closest to the mean in each group were shown (Safranin-O/fast green stain; 200× magnification, scale bar = 50 μm). The specimens from mice treated with NS and control antibody showed remarkably decreased Safranin-O staining and surface irregularities. The TIMP-1 antibody-treated specimens had an irregular superficial layer of cartilage. The surface layer of cartilage in the Sham group was smooth and showed no significant changes; (b) Histologic examination showed a reduced Mankin’s score in the medial femoral condyles of cartilage from mice treated with TIMP-1 antibody. Each value represents the means ± 95% confidence intervals. Significant difference in scores was observed between control Ab and anti-TIMP-1 Ab groups (p = 0.0011); (c) Representative sections of synovium which scores were the most close to the means in each group were shown (hematoxylin and eosin stain; 200× magnification, scale bar = 50 μm). Synovia in the NS- and control antibody-treated mice showed hyperplasia and hypertrophy of synovial lining cells. The TIMP-1 antibody-treated specimens showed slightly more cell proliferation in the synovial lining and cell infiltration than did the sham-operated specimens; and (d) Histologic examination showed a reduced synovitis score in the synovial tissues of knees from mice treated with TIMP-1 antibody. Each value represents the means ± 95% confidence intervals. Significant difference in scores was observed between control Ab and anti-TIMP-1 Ab groups (p = 0.003).
Mentions: To investigate the role of TIMP-1 in the OA, we inhibited the local expression of TIMP-1 when OA was induced. One week after surgery, TIMP-1 neutralization antibody was intraarticularly injected in the OA knees of mice (0.5 mg/kg) once a week for two consecutive weeks. 30 days at sacrifice, cartilages from the mice treated with either NS (normal saline) or an isotype-matched goat IgG antibody (control Ab) showed a remarkably reduction of Safranio-O staining and loss of chondrocytes of surface layer cells (Figure 7a). Nevertheless, in the joints treated with anti-TIMP-1 antibody (anti-TIMP-1 Ab), the severity of lesion was reduced. Slight reduction of Safranin-O staining and some chondrocytes cloning were observed on the superficial layer of cartilage. In the sham-operated knee joints, most of the articular cartilage of the femur had a smooth surface, evenly stained with Safranin-O. The Mankin’s score in the anti-TIMP-1 Ab-treated joints was significantly lower than that in the control Ab-treated ones [5.5 (4.18–6.82) vs. 9.0 (7.54–10.46), p = 0.0011, Figure 7b]. Synovia in NS and control Ab treated-group mice showed hyperplasia and hypertrophy of the lining cells and increased infiltration of inflammatory cells. As compared with the sham-operated group, a slight increase of synovial lining cell proliferation and inflammatory cell infiltration was noted in the anti-TIMP-1 Ab-treated group mice (Figure 7c). The synovitis score in joints treated with anti-TIMP-1 Ab was significantly lower than that treated with control Ab [6.7 (5.02–8.38) vs. 11.1 (8.72–13.48), p = 0.003, Figure 7d]. The intra class coefficients of both scores used for evaluating interobserver’s variation was 0.82, p < 0.001. Taken together, these results indicated that the expression of TIMP-1 increased in the cartilage and synovium of OA mice. Inhibiting its expression could retard the disease progression and attenuate the severity of OA.

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