Halofuginone attenuates articular cartilage degeneration by inhibition of elevated TGF-β1 signaling in articular cartilage in a rodent osteoarthritis model

被引:8
作者
Mu, Wenbo [1 ]
Xu, Boyong [1 ]
Ma, Hairong [1 ,2 ]
Ji, Baochao [1 ]
Zhang, Zhendong [1 ]
Li, Jiao [1 ]
Amat, Abdusami [1 ]
Cao, Li [1 ]
机构
[1] Xinjiang Med Univ, Affiliated Hosp 1, Dept Orthopaed, 137 South Liyushan Rd, Urumqi 830054, Xinjiang, Peoples R China
[2] Xinjiang Med Univ, Affiliated Hosp 1, Clin Med Res Inst, Urumqi 830054, Xinjiang, Peoples R China
基金
中国国家自然科学基金;
关键词
osteoarthritis; articular artilage; TGF-beta; 1; elevation; halofuginone; GROWTH-FACTOR-BETA; VERSUS-HOST-DISEASE; GENE-EXPRESSION; UP-REGULATION; CHONDROCYTES; FIBROSIS; BONE; DIFFERENTIATION; PATHOGENESIS; INFLAMMATION;
D O I
10.3892/mmr.2017.7549
中图分类号
R73 [肿瘤学];
学科分类号
100214 ;
摘要
Osteoarthritis (OA) is the most common degenerative condition of the weight-bearing joints worldwide without effective medical therapy. In order to investigate whether administration of halofuginone (HF) may attenuate OA, the present study allocated 3-month-old male mice into Sham group, vehicle-treated anterior cruciate ligament transection (ACLT) group and HF-treated ACLT group. The present study determined that HF treatment reduced the expression of matrix metallopeptidase-13 and collagen X in articular cartilage. Additionally, it lowered the Osteoarthritis Research Society International-Modified Mankin score and prevented the loss of articular cartilage from Safranin O and Fast Green staining. HF reduced the progression of osteoarthritis by downregulating abnormally elevated TGF-beta 1 activity in articular cartilage. Administration of HF may be a potential preventive therapy for OA.
引用
收藏
页码:7679 / 7684
页数:6
相关论文
共 36 条
[1]   TGF-BETA-1 PREVENTS HYPERTROPHY OF EPIPHYSEAL CHONDROCYTES - REGULATION OF GENE-EXPRESSION FOR CARTILAGE MATRIX PROTEINS AND METALLOPROTEASES [J].
BALLOCK, RT ;
HEYDEMANN, A ;
WAKEFIELD, LM ;
FLANDERS, KC ;
ROBERTS, AB ;
SPORN, MB .
DEVELOPMENTAL BIOLOGY, 1993, 158 (02) :414-429
[2]   Osteoarthritis: an update with relevance for clinical practice [J].
Bijlsma, Johannes W. J. ;
Berenbaum, Francis ;
Lafeber, Foris P. J. G. .
LANCET, 2011, 377 (9783) :2115-2126
[3]   Knee replacement [J].
Carr, Andrew J. ;
Robertsson, Otto ;
Graves, Stephen ;
Price, Andrew J. ;
Arden, Nigel K. ;
Judge, Andrew ;
Beard, David J. .
LANCET, 2012, 379 (9823) :1331-1340
[4]   The transforming growth factor-β superfamily of receptors [J].
de Caestecker, M .
CYTOKINE & GROWTH FACTOR REVIEWS, 2004, 15 (01) :1-11
[5]   Phase I and pharmacokinetic study of halofuginone, an oral quinazolinone derivative in patients with advanced solid tumours [J].
de Jonge, M. J. A. ;
Dumez, H. ;
Verweij, J. ;
Yarkoni, S. ;
Snyder, D. ;
Lacombe, D. ;
Marreaud, S. ;
Yamaguchi, T. ;
Punt, C. J. A. ;
van Oosterom, A. .
EUROPEAN JOURNAL OF CANCER, 2006, 42 (12) :1768-1774
[6]   Hypertrophic differentiation of chondrocytes in osteoarthritis: the developmental aspect of degenerative joint disorders [J].
Dreier, Rita .
ARTHRITIS RESEARCH & THERAPY, 2010, 12 (05)
[7]   TRANSFORMING GROWTH FACTOR-BETA-1 (TGF-BETA-1) UP-REGULATION OF COLLAGEN TYPE-II IN PRIMARY CULTURES OF RABBIT ARTICULAR CHONDROCYTES (RAC) INVOLVES INCREASED MESSENGER-RNA LEVELS WITHOUT AFFECTING MESSENGER-RNA STABILITY AND PROCOLLAGEN PROCESSING [J].
GALERA, P ;
VIVIEN, D ;
PRONOST, S ;
BONAVENTURE, J ;
REDINI, F ;
LOYAU, G ;
PUJOL, JP .
JOURNAL OF CELLULAR PHYSIOLOGY, 1992, 153 (03) :596-606
[8]   Articular cartilage and subchondral bone in the pathogenesis of osteoarthritis [J].
Goldring, Mary B. ;
Goldring, Steven R. .
SKELETAL BIOLOGY AND MEDICINE, 2010, 1192 :230-237
[9]   Changes in the osteochondral unit during osteoarthritis: structure, function and cartilage-bone crosstalk [J].
Goldring, Steven R. ;
Goldring, Mary B. .
NATURE REVIEWS RHEUMATOLOGY, 2016, 12 (11) :632-644
[10]   Analysis of relative gene expression data using real-time quantitative PCR and the 2-ΔΔCT method [J].
Livak, KJ ;
Schmittgen, TD .
METHODS, 2001, 25 (04) :402-408