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Death of chondrocytes in Kashin-Beck disease: Apoptosis, necrosis or necroptosis?
Int J Exp Pathol. 2018 12; 99(6):312-322.IJ

Abstract

The purpose of this paper was to investigate chondrocyte distribution and death in the cartilage in Kashin-Beck disease (KBD). Apoptotic chondrocytes were detected by TUNEL assay. Ultrastructural changes were examined by transmission electron microscope (TEM). Biochemical markers associated with apoptosis (eg, caspase-3) and necroptosis (eg, RIP3) were investigated by immunohistochemistry. In KBD cartilage chondrocyte death was characterized by paler staining of the cells. Multiple chondral cell clusters surrounded the areas lacking cells in the deep zone. The per cent of TUNEL-positive and RIP3-positive chondrocytes were higher in the middle zones of KBD samples; however, there was some positive staining for TUNEL but negative staining for caspase-3. Immunohistochemistry failed to detect significant differences in caspase-3 levels in KBD children compared to controls, suggesting that beside apoptosis necroptosis dominates as a cell death mechanism in the middle zone of cartilage from KBD children. To clarify further the presence of chondrocyte necroptosis in KBD, we performed TUNEL, caspase-3 and RIP3 staining in a rat KBD model which is based upon T-2 toxin treatment under selenium-deficient conditions. Apoptosis and necroptosis co-existed in the middle zone in this rat KBD model. Ultrastructural analysis of chondrocyte from deep cartilage revealed abnormal cells with numerous morphological changes, such as plasma membrane breakdown, generalized swelling of the cytoplasm and loss of identifiable organelles. Chondrocyte death by necrosis in the deep zone of cartilages in KBD may be a result of exposure to T-2 toxin from bone marrow or bloodstream under selenium-deficient nutrition status in KBD endemic areas. Chondrocyte death plays a key role in either the initiation or the progression of KBD pathogenesis.

Authors+Show Affiliations

School of Public Health, Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases of National Health Commission, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China.School of Public Health, Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases of National Health Commission, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China.School of Public Health, Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases of National Health Commission, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China.School of Public Health, Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases of National Health Commission, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China.School of Public Health, Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases of National Health Commission, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China.School of Public Health, Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases of National Health Commission, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China.School of Public Health, Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases of National Health Commission, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China.School of Public Health, Health Science Center, Key Laboratory of Trace Elements and Endemic Diseases of National Health Commission, Xi'an Jiaotong University, Xi'an, 710061, Shaanxi, People's Republic of China.

Pub Type(s)

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

Language

eng

PubMed ID

30680829

Citation

Zhang, Ying, et al. "Death of Chondrocytes in Kashin-Beck Disease: Apoptosis, Necrosis or Necroptosis?" International Journal of Experimental Pathology, vol. 99, no. 6, 2018, pp. 312-322.
Zhang Y, He Y, Zhang D, et al. Death of chondrocytes in Kashin-Beck disease: Apoptosis, necrosis or necroptosis? Int J Exp Pathol. 2018;99(6):312-322.
Zhang, Y., He, Y., Zhang, D., Zhang, M., Wang, M., Zhang, Y., Ma, T., & Chen, J. (2018). Death of chondrocytes in Kashin-Beck disease: Apoptosis, necrosis or necroptosis? International Journal of Experimental Pathology, 99(6), 312-322. https://doi.org/10.1111/iep.12297
Zhang Y, et al. Death of Chondrocytes in Kashin-Beck Disease: Apoptosis, Necrosis or Necroptosis. Int J Exp Pathol. 2018;99(6):312-322. PubMed PMID: 30680829.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Death of chondrocytes in Kashin-Beck disease: Apoptosis, necrosis or necroptosis? AU - Zhang,Ying, AU - He,Ying, AU - Zhang,Dan, AU - Zhang,Meng, AU - Wang,Mengying, AU - Zhang,Ying, AU - Ma,Tianyou, AU - Chen,Jinghong, Y1 - 2019/01/24/ PY - 2018/04/24/received PY - 2018/11/19/revised PY - 2018/11/22/accepted PY - 2019/1/27/pubmed PY - 2019/3/15/medline PY - 2019/1/26/entrez KW - Kashin-Beck disease KW - apoptosis KW - chondrocyte KW - necroptosis KW - necrosis SP - 312 EP - 322 JF - International journal of experimental pathology JO - Int J Exp Pathol VL - 99 IS - 6 N2 - The purpose of this paper was to investigate chondrocyte distribution and death in the cartilage in Kashin-Beck disease (KBD). Apoptotic chondrocytes were detected by TUNEL assay. Ultrastructural changes were examined by transmission electron microscope (TEM). Biochemical markers associated with apoptosis (eg, caspase-3) and necroptosis (eg, RIP3) were investigated by immunohistochemistry. In KBD cartilage chondrocyte death was characterized by paler staining of the cells. Multiple chondral cell clusters surrounded the areas lacking cells in the deep zone. The per cent of TUNEL-positive and RIP3-positive chondrocytes were higher in the middle zones of KBD samples; however, there was some positive staining for TUNEL but negative staining for caspase-3. Immunohistochemistry failed to detect significant differences in caspase-3 levels in KBD children compared to controls, suggesting that beside apoptosis necroptosis dominates as a cell death mechanism in the middle zone of cartilage from KBD children. To clarify further the presence of chondrocyte necroptosis in KBD, we performed TUNEL, caspase-3 and RIP3 staining in a rat KBD model which is based upon T-2 toxin treatment under selenium-deficient conditions. Apoptosis and necroptosis co-existed in the middle zone in this rat KBD model. Ultrastructural analysis of chondrocyte from deep cartilage revealed abnormal cells with numerous morphological changes, such as plasma membrane breakdown, generalized swelling of the cytoplasm and loss of identifiable organelles. Chondrocyte death by necrosis in the deep zone of cartilages in KBD may be a result of exposure to T-2 toxin from bone marrow or bloodstream under selenium-deficient nutrition status in KBD endemic areas. Chondrocyte death plays a key role in either the initiation or the progression of KBD pathogenesis. SN - 1365-2613 UR - https://www.unboundmedicine.com/medline/citation/30680829/Death_of_chondrocytes_in_Kashin_Beck_disease:_Apoptosis_necrosis_or_necroptosis L2 - https://doi.org/10.1111/iep.12297 DB - PRIME DP - Unbound Medicine ER -