Presentation is loading. Please wait.

Presentation is loading. Please wait.

Trichostatin A, a histone deacetylase inhibitor, suppresses synovial inflammation and subsequent cartilage destruction in a collagen antibody-induced.

Published byHarriet Wilson Modified over 5 years ago

Similar presentations

Presentation on theme: "Trichostatin A, a histone deacetylase inhibitor, suppresses synovial inflammation and subsequent cartilage destruction in a collagen antibody-induced."— Presentation transcript:

1 Trichostatin A, a histone deacetylase inhibitor, suppresses synovial inflammation and subsequent cartilage destruction in a collagen antibody-induced arthritis mouse model  Y. Nasu, M.D., K. Nishida, M.D., Ph.D., S. Miyazawa, M.D., Ph.D., T. Komiyama, M.D., Y. Kadota, M.D., N. Abe, M.D., Ph.D., A. Yoshida, S. Hirohata, M.D., Ph.D., A. Ohtsuka, M.D., Ph.D., T. Ozaki, M.D., Ph.D.  Osteoarthritis and Cartilage  Volume 16, Issue 6, Pages (June 2008) DOI: /j.joca Copyright © 2007 Osteoarthritis Research Society International Terms and Conditions

2 Fig. 1 Arthritis induction in mice and the effects of TSA. (A) The arthritis induction and TSA treatment protocol. Sampling 1: sections for immunohistochemistry. Sampling 2: histological evaluation of arthritis and cartilage destruction. (B) Severity of the clinical signs in untreated (CAIA) and TSA-treated mice (see Methods for scoring system). TSA treatment had a dose-dependent inhibitory effect against CAIA. (C) Body weight changes by group. After the onset of clinical arthritis, all mice lost a small amount of weight. No significant differences were observed among the groups. Data are expressed as the means (symbols)±s.e.m. (error bars) (*P<0.05 and **P<0.001 by Bonferroni/Dunn analysis). Osteoarthritis and Cartilage  , DOI: ( /j.joca ) Copyright © 2007 Osteoarthritis Research Society International Terms and Conditions

3 Fig. 2 Histological evaluation of arthritis. The severity of synovial inflammation was evaluated histologically in the specimens obtained on Day 15. Representative results showing the histological appearance of the hind paws are seen in the upper panel. The control group specimens showed synovial hyperplasia, inflammatory cells proliferation, pannus formation, and bone destruction. Joint pathology was less severe in TSA-treated mice. Arrows: synovial hyperplasia, asterisk: joint space. Original magnification: 100×. The mean synovial inflammation score was significantly lower in the TSA 1.0mg/kg and TSA 2.0mg/kg groups than in the control group (n=6). Error bars express ±s.e.m. (*P<0.01 and **P<0.001 by Bonferroni/Dunn analysis). Osteoarthritis and Cartilage  , DOI: ( /j.joca ) Copyright © 2007 Osteoarthritis Research Society International Terms and Conditions

4 Fig. 3 Inhibition of cartilage destruction by TSA treatment. Representative photographs of each grade of cartilage destruction, grade 4 in the control group, grade 3 in the TSA 0.5mg/kg group, grade 2 in the TSA 1.0mg/kg group, and grade 1 in the TSA 2.0mg/kg group. Original magnification: 400×. The total cartilage destruction score was significantly lower in the TSA 1.0mg/kg and TSA 2.0mg/kg groups than in the control group (n=6 each). Error bars express ±s.e.m. (*P<0.001 by Bonferroni/Dunn analysis). Osteoarthritis and Cartilage  , DOI: ( /j.joca ) Copyright © 2007 Osteoarthritis Research Society International Terms and Conditions

5 Fig. 4 Immunohistochemical staining of MMP-3, MMP-13, and TIMP-1 in joint cartilage. The number of MMP-3 and MMP-13-positive chondrocytes was significantly lower in the TSA 2.0mg/kg group (n=5) than in the control group (n=5). In contrast, TIMP-1 was strongly expressed in the joint cartilage obtained from the TSA 2.0mg/kg group. The population of TIMP-1-positive chondrocytes was significantly higher in the TSA 2.0mg/kg group than in the control group. Representative immunohistochemistry results are shown in the upper panels. Error bars express ±SD (*P<0.01, **P<0.001 by Mann–Whitney U test). Osteoarthritis and Cartilage  , DOI: ( /j.joca ) Copyright © 2007 Osteoarthritis Research Society International Terms and Conditions

6 Fig. 5 Immunohistochemical staining for acetyl-histone H4. Cartilage specimens obtained from the control and TSA 2.0mg/kg groups (n=5 each) were positive for acetyl-histone H4 (left panels). The number of acetyl-histone H4-positive cells was higher in the TSA 2.0mg/kg group than in the control group. Error bars express ±SD (*P<0.05 by Mann–Whitney U test). Osteoarthritis and Cartilage  , DOI: ( /j.joca ) Copyright © 2007 Osteoarthritis Research Society International Terms and Conditions

7 Fig. 6 Effect of pro-inflammatory cytokine and TSA on the morphology and gene expression of murine ATDC5 chondrogenic cells. (A) Morphologic features of ATDC5 cells examined by phase-contrast microscopy. No differences were observed in the TSA-treated cells compared with non-stimulated or cytokine-stimulated cells. Original magnification: 200×. (B) The effect of cytokine stimulation and TSA treatment on the expression of type II collagen (Col2a1), aggrecan examined by RT-PCR. TSA did not show the significant catabolic effect on type II collagen and aggrecan expression. (C) The effect of cytokine stimulation and TSA treatment on the expression of MMP-3 and -13 mRNA by ATDC5 examined by real-time PCR. Cytokine-induced expression of MMP-3, but not MMP-13 was significantly suppressed by TSA treatment. All values are averages in triplicated tests. Error bars express ±SD (*P<0.05 by Mann–Whitney U test, n.s.: not significant). Osteoarthritis and Cartilage  , DOI: ( /j.joca ) Copyright © 2007 Osteoarthritis Research Society International Terms and Conditions

Download ppt "Trichostatin A, a histone deacetylase inhibitor, suppresses synovial inflammation and subsequent cartilage destruction in a collagen antibody-induced."

Similar presentations

Trichostatin A, a histone deacetylase inhibitor, suppresses synovial inflammation and subsequent cartilage destruction in a collagen antibody-induced.

Trichostatin A, a histone deacetylase inhibitor, suppresses synovial inflammation and subsequent cartilage destruction in a collagen antibody-induced.
CXC chemokine ligand 12a enhances chondrocyte proliferation and maturation during endochondral bone formation  G.-W. Kim, M.-S. Han, H.-R. Park, E.-J.

CXC chemokine ligand 12a enhances chondrocyte proliferation and maturation during endochondral bone formation  G.-W. Kim, M.-S. Han, H.-R. Park, E.-J.
Involvement of Wnt Signaling in Dermal Fibroblasts

Involvement of Wnt Signaling in Dermal Fibroblasts
MicroRNA-558 regulates the expression of cyclooxygenase-2 and IL-1β-induced catabolic effects in human articular chondrocytes  S.J. Park, E.J. Cheon,

MicroRNA-558 regulates the expression of cyclooxygenase-2 and IL-1β-induced catabolic effects in human articular chondrocytes  S.J. Park, E.J. Cheon,
Chondro-protective effects of low intensity pulsed ultrasound

Chondro-protective effects of low intensity pulsed ultrasound
Time-lapse observation of the dedifferentiation process in mouse chondrocytes using chondrocyte-specific reporters  Y. Minegishi, K. Hosokawa, N. Tsumaki 

Time-lapse observation of the dedifferentiation process in mouse chondrocytes using chondrocyte-specific reporters  Y. Minegishi, K. Hosokawa, N. Tsumaki 
BMP-2 induces the expression of chondrocyte-specific genes in bovine synovium- derived progenitor cells cultured in three-dimensional alginate hydrogel 

BMP-2 induces the expression of chondrocyte-specific genes in bovine synovium- derived progenitor cells cultured in three-dimensional alginate hydrogel 
CCN family 2/connective tissue growth factor (CCN2/CTGF) stimulates proliferation and differentiation of auricular chondrocytes  T. Fujisawa, Ph.D., D.D.S.,

CCN family 2/connective tissue growth factor (CCN2/CTGF) stimulates proliferation and differentiation of auricular chondrocytes  T. Fujisawa, Ph.D., D.D.S.,
Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is increased in osteoarthritis and regulates chondrocyte catabolic and anabolic activities 

Heparin-binding epidermal growth factor-like growth factor (HB-EGF) is increased in osteoarthritis and regulates chondrocyte catabolic and anabolic activities 
Muscle cell-derived factors inhibit inflammatory stimuli-induced damage in hMSC- derived chondrocytes  R.S. Rainbow, H. Kwon, A.T. Foote, R.C. Preda, D.L.

Muscle cell-derived factors inhibit inflammatory stimuli-induced damage in hMSC- derived chondrocytes  R.S. Rainbow, H. Kwon, A.T. Foote, R.C. Preda, D.L.
Optical imaging of mouse articular cartilage using the glycosaminoglycans binding property of fluorescent-labeled octaarginine  K. Inagawa, T. Oohashi,

Optical imaging of mouse articular cartilage using the glycosaminoglycans binding property of fluorescent-labeled octaarginine  K. Inagawa, T. Oohashi,
Insulin-like growth factor-1 boosts the developing process of condylar hyperplasia by stimulating chondrocytes proliferation  Y. Chen, J. Ke, X. Long,

Insulin-like growth factor-1 boosts the developing process of condylar hyperplasia by stimulating chondrocytes proliferation  Y. Chen, J. Ke, X. Long,
MAPKs are essential upstream signaling pathways in proteolytic cartilage degradation – divergence in pathways leading to aggrecanase and MMP-mediated.

MAPKs are essential upstream signaling pathways in proteolytic cartilage degradation – divergence in pathways leading to aggrecanase and MMP-mediated.
A new player in cartilage homeostasis: adiponectin induces nitric oxide synthase type II and pro-inflammatory cytokines in chondrocytes  R. Lago, B.S.,

A new player in cartilage homeostasis: adiponectin induces nitric oxide synthase type II and pro-inflammatory cytokines in chondrocytes  R. Lago, B.S.,
Histone deacetylase inhibitors suppress mechanical stress-induced expression of RUNX-2 and ADAMTS-5 through the inhibition of the MAPK signaling pathway.

Histone deacetylase inhibitors suppress mechanical stress-induced expression of RUNX-2 and ADAMTS-5 through the inhibition of the MAPK signaling pathway.
M. -H. Moon, J. -K. Jeong, Y. -J. Lee, J. -W. Seol, C. J. Jackson, S

M. -H. Moon, J. -K. Jeong, Y. -J. Lee, J. -W. Seol, C. J. Jackson, S
N. Zhong, J. Sun, Z. Min, W. Zhao, R. Zhang, W. Wang, J. Tian, L

N. Zhong, J. Sun, Z. Min, W. Zhao, R. Zhang, W. Wang, J. Tian, L
CXC chemokine ligand 12a enhances chondrocyte proliferation and maturation during endochondral bone formation  G.-W. Kim, M.-S. Han, H.-R. Park, E.-J.

CXC chemokine ligand 12a enhances chondrocyte proliferation and maturation during endochondral bone formation  G.-W. Kim, M.-S. Han, H.-R. Park, E.-J.
Loss of Vhl in cartilage accelerated the progression of age-associated and surgically induced murine osteoarthritis  T. Weng, Y. Xie, L. Yi, J. Huang,

Loss of Vhl in cartilage accelerated the progression of age-associated and surgically induced murine osteoarthritis  T. Weng, Y. Xie, L. Yi, J. Huang,
GRIP1 enhances estrogen receptor α-dependent extracellular matrix gene expression in chondrogenic cells  M. Kato, H. Takaishi, M. Yoda, T. Tohmonda, J.

GRIP1 enhances estrogen receptor α-dependent extracellular matrix gene expression in chondrogenic cells  M. Kato, H. Takaishi, M. Yoda, T. Tohmonda, J.

Similar presentations

Ads by Google