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Intermittent cyclic mechanical tension promotes endplate cartilage degeneration via canonical Wnt signaling pathway and E-cadherin/β-catenin complex cross-talk.
Osteoarthritis Cartilage 2016; 24(1):158-68OC

Abstract

OBJECTIVE

This study aimed to investigate the role of the Wnt/β-catenin signaling pathway and E-cadherin/β-catenin complex in intermittent cyclic mechanical tension (ICMT)-induced endplate cartilage degeneration.

DESIGN

β-Catenin expression was measured in disc samples obtained from patients with disc degeneration and those with cervical vertebrae fracture or dislocation. Histological staining was performed to examine the disc tissue morphology and extracellular matrix after application of ICMT in vitro and in vivo. Multiple strategies were employed to examine activation of Wnt/β-catenin signaling after ICMT application in vivo and in vitro. Co-immunoprecipitation was performed to examine the interaction between E-cadherin and β-catenin. Pathway-specific inhibitors and an E-cadherin expression plasmid were used to regulate Wnt/β-catenin signaling and E-cadherin expression.

RESULTS

β-Catenin protein expression was elevated significantly, whereas cartilaginous genes were down-regulated in endplate cartilage samples obtained from patients with disc degeneration. ICMT loading led to Wnt/β-catenin signaling activation and the loss of the chondrogenic phenotype of endplate chondrocytes in both an in vivo rabbit model and in vitro endplate chondrocyte culture system. Inhibition of Wnt/β-catenin signaling suppressed the decrease in ICMT-induced cartilaginous gene expression. Furthermore, E-cadherin expression was inhibited by ICMT stimulation, resulting in a decrease in the interaction between E-cadherin and β-catenin proteins. Over-expression of E-cadherin rescued the cartilaginous gene expression by enhancing the interaction between E-cadherin and β-catenin proteins.

CONCLUSIONS

ICMT promotes endplate cartilage degeneration via activation of Wnt/β-catenin signaling and suppression of physical protein-protein interactions between E-cadherin and β-catenin.

Authors+Show Affiliations

Department of Orthopedic Surgery, Yijishan Hospital, Wannan Medical College, Wuhu, 241001, Anhui, China. Electronic address: xuhg@medmail.com.cn.Department of Orthopedic Surgery, Yijishan Hospital, Wannan Medical College, Wuhu, 241001, Anhui, China.Department of Orthopedic Surgery, Chinese Medicine Hospitals of Wuhu, Wuhu, 241001, Anhui, China.Department of Cell Biology and Genetics, Zunyi Medical College, Zunyi, 563003, Guizhou, China.Department of Orthopedic Surgery, Yijishan Hospital, Wannan Medical College, Wuhu, 241001, Anhui, China.Department of Orthopedic Surgery, Yijishan Hospital, Wannan Medical College, Wuhu, 241001, Anhui, China.Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200011, China.Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200011, China.Shanghai Key Laboratory of Orthopaedic Implants, Department of Orthopaedic Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, 200011, China. Electronic address: xlzhang@sibs.ac.cn.

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

26247612

Citation

Xu, H-g, et al. "Intermittent Cyclic Mechanical Tension Promotes Endplate Cartilage Degeneration Via Canonical Wnt Signaling Pathway and E-cadherin/β-catenin Complex Cross-talk." Osteoarthritis and Cartilage, vol. 24, no. 1, 2016, pp. 158-68.
Xu HG, Zheng Q, Song JX, et al. Intermittent cyclic mechanical tension promotes endplate cartilage degeneration via canonical Wnt signaling pathway and E-cadherin/β-catenin complex cross-talk. Osteoarthr Cartil. 2016;24(1):158-68.
Xu, H. G., Zheng, Q., Song, J. X., Li, J., Wang, H., Liu, P., ... Zhang, X. L. (2016). Intermittent cyclic mechanical tension promotes endplate cartilage degeneration via canonical Wnt signaling pathway and E-cadherin/β-catenin complex cross-talk. Osteoarthritis and Cartilage, 24(1), pp. 158-68. doi:10.1016/j.joca.2015.07.019.
Xu HG, et al. Intermittent Cyclic Mechanical Tension Promotes Endplate Cartilage Degeneration Via Canonical Wnt Signaling Pathway and E-cadherin/β-catenin Complex Cross-talk. Osteoarthr Cartil. 2016;24(1):158-68. PubMed PMID: 26247612.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Intermittent cyclic mechanical tension promotes endplate cartilage degeneration via canonical Wnt signaling pathway and E-cadherin/β-catenin complex cross-talk. AU - Xu,H-g, AU - Zheng,Q, AU - Song,J-x, AU - Li,J, AU - Wang,H, AU - Liu,P, AU - Wang,J, AU - Wang,C-d, AU - Zhang,X-l, Y1 - 2015/08/03/ PY - 2014/11/11/received PY - 2015/07/20/revised PY - 2015/07/27/accepted PY - 2015/8/7/entrez PY - 2015/8/8/pubmed PY - 2016/9/27/medline KW - Degeneration KW - E-cadherin KW - Endplate cartilage KW - Mechanical tension KW - β-catenin SP - 158 EP - 68 JF - Osteoarthritis and cartilage JO - Osteoarthr. Cartil. VL - 24 IS - 1 N2 - OBJECTIVE: This study aimed to investigate the role of the Wnt/β-catenin signaling pathway and E-cadherin/β-catenin complex in intermittent cyclic mechanical tension (ICMT)-induced endplate cartilage degeneration. DESIGN: β-Catenin expression was measured in disc samples obtained from patients with disc degeneration and those with cervical vertebrae fracture or dislocation. Histological staining was performed to examine the disc tissue morphology and extracellular matrix after application of ICMT in vitro and in vivo. Multiple strategies were employed to examine activation of Wnt/β-catenin signaling after ICMT application in vivo and in vitro. Co-immunoprecipitation was performed to examine the interaction between E-cadherin and β-catenin. Pathway-specific inhibitors and an E-cadherin expression plasmid were used to regulate Wnt/β-catenin signaling and E-cadherin expression. RESULTS: β-Catenin protein expression was elevated significantly, whereas cartilaginous genes were down-regulated in endplate cartilage samples obtained from patients with disc degeneration. ICMT loading led to Wnt/β-catenin signaling activation and the loss of the chondrogenic phenotype of endplate chondrocytes in both an in vivo rabbit model and in vitro endplate chondrocyte culture system. Inhibition of Wnt/β-catenin signaling suppressed the decrease in ICMT-induced cartilaginous gene expression. Furthermore, E-cadherin expression was inhibited by ICMT stimulation, resulting in a decrease in the interaction between E-cadherin and β-catenin proteins. Over-expression of E-cadherin rescued the cartilaginous gene expression by enhancing the interaction between E-cadherin and β-catenin proteins. CONCLUSIONS: ICMT promotes endplate cartilage degeneration via activation of Wnt/β-catenin signaling and suppression of physical protein-protein interactions between E-cadherin and β-catenin. SN - 1522-9653 UR - https://www.unboundmedicine.com/medline/citation/26247612/Intermittent_cyclic_mechanical_tension_promotes_endplate_cartilage_degeneration_via_canonical_Wnt_signaling_pathway_and_E_cadherin/β_catenin_complex_cross_talk_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1063-4584(15)01262-5 DB - PRIME DP - Unbound Medicine ER -