Activation of β-catenin signaling in aggrecan-expressing cells in temporomandibular joint causes osteoarthritis-like defects.
10.1038/s41368-018-0016-z
- Author:
Tianqian HUI
1
;
Yachuan ZHOU
2
;
Tingyu WANG
3
;
Jun LI
2
;
Shanxing ZHANG
2
;
Lifan LIAO
2
;
Jianhong GU
2
;
Ling YE
4
;
Lan ZHAO
2
;
Di CHEN
5
Author Information
1. Department of Pediatric Dentistry, Peking University School and Hospital of Stomatology, Beijing, China.
2. Department of Orthopaedic Surgery, Rush University Medical Center, Chicago, USA.
3. Department of Pharmacy, Shanghai Ninth People's Hospital, Shanghai JiaoTong University School of Medicine, Shanghai, China.
4. State Key Laboratory of Oral Diseases & National Clinical Research Center for Oral Diseases & West China Hospital of Stomatology, Sichuan University, Chengdu, China.
5. Department of Orthopaedic Surgery, Rush University Medical Center, Chicago, USA. di_chen@rush.edu.
- Publication Type:Journal Article
- MeSH:
Aggrecans;
metabolism;
Animals;
Apoptosis;
Cartilage, Articular;
metabolism;
Cell Differentiation;
Cell Proliferation;
Cells, Cultured;
Disease Models, Animal;
In Situ Nick-End Labeling;
Mice;
Osteoarthritis;
metabolism;
Phenotype;
Signal Transduction;
Surface Properties;
Temporomandibular Joint;
metabolism;
beta Catenin;
metabolism
- From:
International Journal of Oral Science
2018;10(2):13-13
- CountryChina
- Language:English
-
Abstract:
β-Catenin plays a critical role in cartilage formation and development. To further understand the role of β-catenin in osteoarthritis (OA) development in temporomandibular joint (TMJ), we have generated β-catenin conditional activation mice (β-cat(ex3) ) by breeding Agc1-CreER mice with β-catenin mice. Results of histologic analysis showed the progressive TMJ defects in 3- and 6-month-old β-cat(ex3) mice (tamoxifen induction was performed at 2 weeks of age), including decreased chondrocyte numbers in the superficial layer associated with less Alcian blue staining, increased numbers of hypertrophic chondrocytes in deep layers, and rough articular surface. Compared to the TMJ phenotype of β-cat(ex3) mice, β-cat(ex3) mice showed much severe morphological defects in the superficial layer of TMJ. This may reflect that Agc1-CreER mice could efficiently target cells in the superficial layer of TMJ. Results of immunostaining showed significantly increased expression of MMP13, Col-X, Adamts4, and Adamts5 in TMJ of β-cat(ex3) mice. Results of proliferating cell nuclear antigen (PCNA), Ki67, and terminal deoxinucleotidyl transferase-mediated dUTP-fluorescein nick end labeling (TUNEL) staining further demonstrated that cell proliferation was decreased and cell apoptosis was increased in condylar cartilage of β-cat(ex3) mice. Our findings indicate that abnormal upregulation of β-catenin in TMJ leads to defects assembling to OA-like phenotype, further demonstrating that β-catenin plays a critical role in TMJ pathogenesis.
