PMID- 31762289
OWN - NLM
STAT- MEDLINE
DCOM- 20220329
LR  - 20240405
IS  - 1947-6043 (Electronic)
IS  - 1947-6035 (Print)
IS  - 1947-6035 (Linking)
VI  - 13
IP  - 1_suppl
DP  - 2021 Dec
TI  - DR4-Associated Death Receptor Signal Promotes Cartilage Damage in Patients With 
      Kashin-Beck Disease.
PG  - 789S-796S
LID - 10.1177/1947603519886626 [doi]
AB  - Purpose. To explore the relationship between the death receptor (DR) and the 
      pathological progression of Kashin-Beck disease (KBD). Design. KBD cartilage 
      samples were collected from 15 patients diagnosed according to the "National 
      Diagnostic Criteria of KBD" in China. In vitro monolayer chondrocytes were 
      cultured in complete medium. Caspase-3 and caspase-8 activities in chondrocytes 
      were analyzed using a kit. Nuclear morphology was observed by Hoechst 33258 
      staining, apoptosis was verified by flow cytometry analysis, and DR molecules 
      were detected using Western blotting and quantitative real-time reverse 
      transcription polymerase chain reaction analysis. Results. Early apoptotic rates 
      of KBD and osteoarthritis (OA) chondrocytes were higher than those of normal 
      control (NC) cells. Excessive apoptotic nuclei were observed in OA and KBD cells 
      after Hoechst 33258 staining. Activities of both caspase-3 and caspase-8 were 
      higher in KBD and OA cells than in NC cells. The average DR4 mRNA level in KBD 
      cells was 3.301-fold higher than that in NC cells, Fas-associating protein with 
      death domain (FADD) transcript level in KBD cells was 2.528-fold higher than that 
      in NC cells. Western blot analyses showed that FAS, DR4, DR5, caspase-3, and FADD 
      were upregulated in the KBD and OA groups compared with the NC group. High 
      expression of caspase-8 in KBD compared with NC was verified, whereas cellular 
      FLICE-inhibitory protein (c-FLIP) in KBD was significantly downregulated. 
      Conclusions. KBD and OA chondrocytes showed obvious FADD-caspase-dependent 
      apoptosis, which is related to the DR pathway. Apoptosis in KBD articular 
      cartilage is mainly related to FAS/DR4-FADD-caspase signaling, and OA is 
      associated with FAS/DR4/DR5-FADD-caspase signaling.
FAU - Wu, Shixun
AU  - Wu S
AD  - Department of Orthopedics Surgery, Shaanxi Provincial People's Hospital, Xi'an 
      JiaoTong University, Xi'an, People's Republic of China.
AD  - Institute of Endemic Diseases of School of Public Health, Health Science Center 
      of Xi'an JiaoTong University, NHC Key Laboratory of Trace Elements and Endemic 
      Diseases, Xi'an, Shaanxi, People's Republic of China.
AD  - Collaborative Innovation Center of Endemic Diseases and Health Promotion in Silk 
      Road Region, Xi'an JiaoTong University, Xi'an, People's Republic of China.
FAU - Yi, Zhi
AU  - Yi Z
AD  - Department of Orthopedics Surgery, Shaanxi Provincial People's Hospital, Xi'an 
      JiaoTong University, Xi'an, People's Republic of China.
FAU - Ling, Ming
AU  - Ling M
AD  - Department of Orthopedics Surgery, Shaanxi Provincial People's Hospital, Xi'an 
      JiaoTong University, Xi'an, People's Republic of China.
FAU - Liu, Shizhang
AU  - Liu S
AD  - Department of Orthopedics Surgery, Shaanxi Provincial People's Hospital, Xi'an 
      JiaoTong University, Xi'an, People's Republic of China.
FAU - Sun, Zhengming
AU  - Sun Z
AD  - Department of Orthopedics Surgery, Shaanxi Provincial People's Hospital, Xi'an 
      JiaoTong University, Xi'an, People's Republic of China.
FAU - Guo, Xiong
AU  - Guo X
AD  - Institute of Endemic Diseases of School of Public Health, Health Science Center 
      of Xi'an JiaoTong University, NHC Key Laboratory of Trace Elements and Endemic 
      Diseases, Xi'an, Shaanxi, People's Republic of China.
AD  - Collaborative Innovation Center of Endemic Diseases and Health Promotion in Silk 
      Road Region, Xi'an JiaoTong University, Xi'an, People's Republic of China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191124
PL  - United States
TA  - Cartilage
JT  - Cartilage
JID - 101518378
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
RN  - EC 3.4.22.- (Caspase 3)
RN  - EC 3.4.22.- (Caspase 8)
SB  - IM
MH  - Cartilage, Articular/*metabolism
MH  - Caspase 3/metabolism
MH  - Caspase 8
MH  - Chondrocytes/metabolism
MH  - *Extracellular Matrix
MH  - Humans
MH  - Kashin-Beck Disease/*complications/*metabolism
MH  - Osteoarthritis/*metabolism
MH  - *Receptors, TNF-Related Apoptosis-Inducing Ligand
PMC - PMC8808889
OTO - NOTNLM
OT  - Kashin-Beck disease
OT  - apoptosis
OT  - death receptor
OT  - osteoarthritis
OT  - pathogenesis
COIS- Declaration of Conflicting Interests: The author(s) declared no potential 
      conflicts of interest with respect to the research, authorship, and/or 
      publication of this article.
EDAT- 2019/11/26 06:00
MHDA- 2022/03/30 06:00
PMCR- 2022/06/01
CRDT- 2019/11/26 06:00
PHST- 2019/11/26 06:00 [pubmed]
PHST- 2022/03/30 06:00 [medline]
PHST- 2019/11/26 06:00 [entrez]
PHST- 2022/06/01 00:00 [pmc-release]
AID - 10.1177_1947603519886626 [pii]
AID - 10.1177/1947603519886626 [doi]
PST - ppublish
SO  - Cartilage. 2021 Dec;13(1_suppl):789S-796S. doi: 10.1177/1947603519886626. Epub 
      2019 Nov 24.