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Defective autophagy in chondrocytes with Kashin-Beck disease but higher than osteoarthritis.
Osteoarthritis Cartilage. 2014 Nov; 22(11):1936-46.OC

Abstract

OBJECTIVE

This study was undertaken to monitor autophagy in chondrocytes with Kashin-Beck disease (KBD) and osteoarthritis (OA).

METHODS

The identification and quantification of autophagy were morphologically visualized by transmission electron microscopy (TEM), together with immunohistochemical localization of Beclin1 and LC3 in cartilage, and immunoblotting of cellular Beclin1, LC3 and p62/SQSTM1 in the normal, KBD and OA groups. Sequentially, regulated-autophagy genes (ATG) were analyzed by IPA software and validated by quantitative real-time polymerase chain reaction (qRT-PCR). Cytotoxicity of cell death was measured by fluorescence detection and flow cytometry (FCM). The co-localization and measurement of autophagy and mitochondria/reactive oxygen species (ROS) were carried out.

RESULTS

KBD chondrocytes exhibited a variety of abnormal cellular contents including nuclei, mitochondrial, glycogen deposits and microfilaments, and OA chondrocytes mainly presented swelled endocytoplasmic reticulum (ER). Beclin1 and LC3 were reduced both in KBD and OA compared with normal controls; however, the two proteins and p62 in KBD were in a higher level than OA. Simultaneously, KBD chondrocytes showed 45 genes that were different from normal controls and 92 genes different from OA, whose functions were mainly involved in cell morphology, cellular functions, cell death and survival. Autophagy was negatively correlated with apoptosis in the three kinds of chondrocytes, and the rates decreased when autophagy was induced by rapamycin. Similarly, KBD and OA chondrocytes showed lower autophagy and higher ROS production compared with the normal chondrocytes.

CONCLUSION

Autophagy was defective in KBD chondrocytes, but it was higher than in OA. The insufficient autophagy may be associated with apoptosis and mitochondrial change in the pathogenesis of KBD and OA.

Authors+Show Affiliations

School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Key Laboratory of Trace Elements and Endemic Diseases, Ministry of Health, Xi'an, Shaanxi 710061, China. Electronic address: xj.cy.69@stu.xjtu.edu.cn.School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Key Laboratory of Trace Elements and Endemic Diseases, Ministry of Health, Xi'an, Shaanxi 710061, China. Electronic address: 164857627@qq.com.School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Key Laboratory of Trace Elements and Endemic Diseases, Ministry of Health, Xi'an, Shaanxi 710061, China. Electronic address: yaox_iao@126.com.Department of Respiratory Medicine, Second Affiliated Hospital, Xi'an Jiaotong University, Xi'an 710004, China. Electronic address: yaosha1860@stu.xjtu.edu.cn.Department of Ankle Joint, Hong Hui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an 710054, China. Electronic address: tongrenly@163.com.Department of Joint Surgery, Hong Hui Hospital, Xi'an Jiaotong University Health Science Center, Xi'an 710054, China. Electronic address: sousou369@163.com.School of Public Health, Xi'an Jiaotong University Health Science Center, Key Laboratory of Environment and Genes Related to Diseases, Ministry of Education, Key Laboratory of Trace Elements and Endemic Diseases, Ministry of Health, Xi'an, Shaanxi 710061, China. Electronic address: guox@mail.xjtu.edu.cn.

Pub Type(s)

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

Language

eng

PubMed ID

25168363

Citation

Wu, C, et al. "Defective Autophagy in Chondrocytes With Kashin-Beck Disease but Higher Than Osteoarthritis." Osteoarthritis and Cartilage, vol. 22, no. 11, 2014, pp. 1936-46.
Wu C, Zheng J, Yao X, et al. Defective autophagy in chondrocytes with Kashin-Beck disease but higher than osteoarthritis. Osteoarthr Cartil. 2014;22(11):1936-46.
Wu, C., Zheng, J., Yao, X., Shan, H., Li, Y., Xu, P., & Guo, X. (2014). Defective autophagy in chondrocytes with Kashin-Beck disease but higher than osteoarthritis. Osteoarthritis and Cartilage, 22(11), 1936-46. https://doi.org/10.1016/j.joca.2014.08.010
Wu C, et al. Defective Autophagy in Chondrocytes With Kashin-Beck Disease but Higher Than Osteoarthritis. Osteoarthr Cartil. 2014;22(11):1936-46. PubMed PMID: 25168363.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Defective autophagy in chondrocytes with Kashin-Beck disease but higher than osteoarthritis. AU - Wu,C, AU - Zheng,J, AU - Yao,X, AU - Shan,H, AU - Li,Y, AU - Xu,P, AU - Guo,X, Y1 - 2014/08/27/ PY - 2014/01/31/received PY - 2014/08/09/revised PY - 2014/08/18/accepted PY - 2014/8/30/entrez PY - 2014/8/30/pubmed PY - 2015/11/18/medline KW - Autophagy KW - Cell death KW - Kashin-Beck disease KW - Mitochondria KW - Osteoarthritis SP - 1936 EP - 46 JF - Osteoarthritis and cartilage JO - Osteoarthr. Cartil. VL - 22 IS - 11 N2 - OBJECTIVE: This study was undertaken to monitor autophagy in chondrocytes with Kashin-Beck disease (KBD) and osteoarthritis (OA). METHODS: The identification and quantification of autophagy were morphologically visualized by transmission electron microscopy (TEM), together with immunohistochemical localization of Beclin1 and LC3 in cartilage, and immunoblotting of cellular Beclin1, LC3 and p62/SQSTM1 in the normal, KBD and OA groups. Sequentially, regulated-autophagy genes (ATG) were analyzed by IPA software and validated by quantitative real-time polymerase chain reaction (qRT-PCR). Cytotoxicity of cell death was measured by fluorescence detection and flow cytometry (FCM). The co-localization and measurement of autophagy and mitochondria/reactive oxygen species (ROS) were carried out. RESULTS: KBD chondrocytes exhibited a variety of abnormal cellular contents including nuclei, mitochondrial, glycogen deposits and microfilaments, and OA chondrocytes mainly presented swelled endocytoplasmic reticulum (ER). Beclin1 and LC3 were reduced both in KBD and OA compared with normal controls; however, the two proteins and p62 in KBD were in a higher level than OA. Simultaneously, KBD chondrocytes showed 45 genes that were different from normal controls and 92 genes different from OA, whose functions were mainly involved in cell morphology, cellular functions, cell death and survival. Autophagy was negatively correlated with apoptosis in the three kinds of chondrocytes, and the rates decreased when autophagy was induced by rapamycin. Similarly, KBD and OA chondrocytes showed lower autophagy and higher ROS production compared with the normal chondrocytes. CONCLUSION: Autophagy was defective in KBD chondrocytes, but it was higher than in OA. The insufficient autophagy may be associated with apoptosis and mitochondrial change in the pathogenesis of KBD and OA. SN - 1522-9653 UR - https://www.unboundmedicine.com/medline/citation/25168363/Defective_autophagy_in_chondrocytes_with_Kashin_Beck_disease_but_higher_than_osteoarthritis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1063-4584(14)01223-0 DB - PRIME DP - Unbound Medicine ER -