PMID- 28744712
OWN - NLM
STAT- MEDLINE
DCOM- 20180710
LR  - 20210109
IS  - 1573-2576 (Electronic)
IS  - 0360-3997 (Linking)
VI  - 40
IP  - 6
DP  - 2017 Dec
TI  - Vacuolar Protein Sorting 4B (VPS4B) Regulates Apoptosis of Chondrocytes via p38 
      Mitogen-Activated Protein Kinases (MAPK) in Osteoarthritis.
PG  - 1924-1932
LID - 10.1007/s10753-017-0633-2 [doi]
AB  - To aim of this study is to investigate the expression of VPS4B (vacuolar protein 
      sorting 4B) in articular cartilage with osteoarthritis (OA) and to analyze the 
      relationship between VPS4B and chondrocyte apoptosis. We established an OA rat 
      model by the MLI (meniscal/ligamentous injury) modeling method, and we observed 
      the expression of VPS4B in articular cartilage through immunohistochemistry and 
      reverse transcription polymerase chain reaction (RT-PCR). Human SW1353 
      chondrosarcoma cells were treated with IL-1beta to mimic the OA-like chondrocyte 
      injury in vitro, and Western blot was employed to examine the IL-1beta-induced 
      expression of VPS4B, phosphorylated p38, and apoptotic markers, namely active 
      caspase-3 and cleaved poly (ADP-ribose) polymerase (PARP). The co-localization of 
      VPS4B and active caspase 3 was confirmed through immunofluorescence. We knocked 
      down VPS4B expression through RNA interference. Western blot was carried out to 
      detect the knockdown efficiency of VPS4B and evaluate its effects on 
      IL-1beta-stimulated expression of apoptotic markers and phosphorylated p38 in SW1353 
      cells. Annexin V/propidium iodide (PI) staining was used to detect chondrocyte 
      apoptosis. VPS4B expression was significantly upregulated in articular cartilage 
      of OA rat model. IL-1beta stimulation increased the expression of VPS4B, apoptotic 
      markers, and phosphorylated p38 in SW1353 cells. VPS4B co-localized with active 
      caspase 3 in IL-1beta-treated SW1353 cells. VPS4B inhibition significantly reduced 
      IL-1beta-stimulated expression of apoptotic markers and phosphorylated p38 in SW1353 
      cells. Moreover, flow cytometry assay demonstrated that VPS4B knockdown 
      alleviated IL-1beta-induced apoptosis. Our results suggested that VPS4B might 
      facilitate chondrocyte apoptosis in OA via p38 MAPK signaling pathway. This study 
      may provide a novel insight into the pathophysiology of OA and a potential 
      therapeutic target for its treatment.
FAU - Xu, Libin
AU  - Xu L
AD  - Department of Orthopaedics, Affiliated Taizhou People's Hospital of Nantong 
      University, Yingchun Road, Taizhou, 225300, China.
FAU - Zhai, Leilei
AU  - Zhai L
AD  - Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong 
      University, 20 XiSi Road, Nantong, Jiangsu Province, 226001, China.
FAU - Ge, Qingtian
AU  - Ge Q
AD  - Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong 
      University, 20 XiSi Road, Nantong, Jiangsu Province, 226001, China.
FAU - Liu, Zhongbing
AU  - Liu Z
AD  - Department of Orthopaedics, Affiliated Taizhou People's Hospital of Nantong 
      University, Yingchun Road, Taizhou, 225300, China.
FAU - Tao, Ran
AU  - Tao R
AD  - Department of Orthopaedics, Affiliated Hospital of Nantong University, Nantong 
      University, 20 XiSi Road, Nantong, Jiangsu Province, 226001, China. 
      ambitiontom@163.com.
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Inflammation
JT  - Inflammation
JID - 7600105
RN  - 0 (Endosomal Sorting Complexes Required for Transport)
RN  - 0 (Interleukin-1beta)
RN  - EC 2.7.11.24 (p38 Mitogen-Activated Protein Kinases)
RN  - EC 3.6.4.- (ATPases Associated with Diverse Cellular Activities)
RN  - EC 3.6.4.6 (VPS4B protein, human)
SB  - IM
MH  - ATPases Associated with Diverse Cellular Activities/metabolism/*physiology
MH  - Animals
MH  - *Apoptosis/drug effects
MH  - Cartilage, Articular/pathology
MH  - Cell Line
MH  - Chondrocytes/*pathology
MH  - Endosomal Sorting Complexes Required for Transport/metabolism/*physiology
MH  - Humans
MH  - Interleukin-1beta/pharmacology
MH  - Osteoarthritis/*pathology
MH  - Rats
MH  - p38 Mitogen-Activated Protein Kinases/*metabolism
OTO - NOTNLM
OT  - interleukin-1beta
OT  - osteoarthritis apoptosis
OT  - phosphorylated p38
OT  - vPS4B
EDAT- 2017/07/27 06:00
MHDA- 2018/07/11 06:00
CRDT- 2017/07/27 06:00
PHST- 2017/07/27 06:00 [pubmed]
PHST- 2018/07/11 06:00 [medline]
PHST- 2017/07/27 06:00 [entrez]
AID - 10.1007/s10753-017-0633-2 [pii]
AID - 10.1007/s10753-017-0633-2 [doi]
PST - ppublish
SO  - Inflammation. 2017 Dec;40(6):1924-1932. doi: 10.1007/s10753-017-0633-2.