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Enhancement of chondrocyte autophagy is an early response in the degenerative cartilage of the temporomandibular joint to biomechanical dental stimulation

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Abstract

Autophagy is a cell protective mechanism for maintaining cellular homeostasis. The present study aimed to investigate whether autophagy is enhanced in the biomechanically induced degenerative cartilage of the temporomandibular joint (TMJ) and the potential role of mitogen-activated protein kinase kinase kinase kinase 3 (MAP4K3) and mammalian Target of rapamycin (mTOR) in this observation. To induce degenerative changes in the TMJs, rats were subjected to biomechanical dental stimulation by moving 4 molars away from their original position as we previously reported. The ultrastructure of autophagosome was observed by transmission electron microscopy. The number of lysosomes was analyzed by flow cytometry. The expression levels of Beclin1 and LC3 and the involvement of MAP4K3 activity were detected by immunohistochemistry, real-time PCR and western blot. The activity of the mTOR pathway indicated by p-mTOR and p-p70S6 K was assayed by western blot. TMJ degeneration, characterized by irregular cell arrangement and cell-free area, was induced in the experimental groups. Under transmission electron microscopy, we observed the presence of autophagosomes, small patches of condensed chromatin, abundant rough endoplasmic reticulum and Golgi apparatus. The number of lysosomes and the expression levels of Beclin1 and LC3 increased, while the activity of mTOR and the expression level of MAP4K3 decreased in the experimental groups. Cartilage in TMJ which was induced to be degenerative biomechanically exhibited autophagy accompanied by reduced mTOR and MAP4K3 activity.

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Abbreviations

LC3:

Light chain 3

mTOR:

Mammalian target of rapamycin

OA:

Osteoarthritis

ROS:

Reactive oxygen species

TMJ:

Temporomandibular joint

TMD:

Temporomandibular disorders

ULK:

Uncoordinated-51 like kinase

MAP4K3:

Mitogen-activated protein kinase kinase kinase kinase 3

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Acknowledgments

We thank Shujing Cai for assistance with the establishment of model rats and Jintao Hu, Department of Immunology, Fourth Military Medical University for assistance with flow cytometry analysis. This work was supported by grants from the National Natural Science Foundation of China (No. 30772429, No. 30801315 and No.81271169).

Conflict of interest

The authors declare that they have no conflict of interest.

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Authors and Affiliations

  1. Department of Oral Anatomy and Physiology and TMD, School of Stomatology, Fourth Military Medical University, 145 Changlexi Road, Xi’an, 710032, China

    Mian Zhang, Jing Zhang, Lei Lu, Zhong-Ying Qiu, Xu Zhang, Shi-Bin Yu & Mei-Qing Wang

  2. Department of Orthopaedics, Xijing Hospital, Fourth Military Medical University, 145 Changlexi Road, Xi’an, 710032, China

    Yao-Ping Wu

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  1. Mian Zhang
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Correspondence to Mei-Qing Wang.

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Zhang, M., Zhang, J., Lu, L. et al. Enhancement of chondrocyte autophagy is an early response in the degenerative cartilage of the temporomandibular joint to biomechanical dental stimulation. Apoptosis 18, 423–434 (2013). https://doi.org/10.1007/s10495-013-0811-0

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