PMID- 30685956
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20200930
IS  - 1976-1902 (Print)
IS  - 1976-7846 (Electronic)
IS  - 1976-1902 (Linking)
VI  - 13
IP  - 3
DP  - 2019 Jun
TI  - Angiopoietin-Like Protein 2 Induces Synovial Inflammation in the Facet Joint 
      Leading to Degenerative Changes via Interleukin-6 Secretion.
PG  - 368-376
LID - 10.31616/asj.2018.0178 [doi]
AB  - STUDY DESIGN: Experimental human study. PURPOSE: To determine whether 
      angiopoietin-like protein 2 (ANGPTL2) is highly expressed in the hyperplastic 
      facet joint (FJ) synovium and whether it activates interleukin-6 (IL-6) secretion 
      in FJ synoviocytes. OVERVIEW OF LITERATURE: Mechanical stress-induced synovitis 
      is partially, but significantly, responsible for degenerative and subsequently 
      osteoarthritic changes in the FJ tissues in patients with lumbar spinal stenosis 
      (LSS). However, the underlying molecular mechanism remains unclear. IL-6 is 
      highly expressed in degenerative FJ synovial tissue and is responsible for local 
      chronic inflammation. ANGPTL2, an inflammatory and mechanically induced mediator, 
      promotes the expression of IL-6 in many cells. METHODS: FJ tissues were harvested 
      from five patients who had undergone lumbar surgery. Immunohistochemistry for 
      ANGPTL2, IL-6, and cell markers was performed in the FJ tissue samples. After 
      cultured synoviocytes from the FJ tissues were subjected to mechanical stress, 
      ANGPTL2 expression and secretion were measured quantitatively using real-time 
      quantitative reverse-transcription-polymerase chain reaction and enzyme-linked 
      immunosorbent assay (ELISA), respectively. Following ANGPTL2 administration in 
      the FJ synoviocytes, anti-nuclear factor-kappaB (NF-kappaB) activation was investigated 
      using immunocytochemistry, and IL-6 expression and secretion were assayed 
      quantitatively with or without NF-kappaB inhibitor. Moreover, we assessed whether 
      ANGPTL2-induced IL-6 modulates leucocyte recruitment in the degenerative process 
      by focusing on the monocyte chemoattractant protein-1 (MCP-1) expression. 
      RESULTS: ANGPTL2 and IL-6 were highly expressed in the hyperplastic FJ synovium 
      samples. ANGPTL2 was co-expressed in both, fibroblast-like and macrophage-like 
      synoviocytes. Further, the expression and secretion of ANGPTL2 in the FJ 
      synoviocytes increased in response to stimulation by mechanical stretching. 
      ANGPTL2 protein promoted the nuclear translocation of NF-kappaB and induced IL-6 
      expression and secretion in the FJ synoviocytes. This effect was reversed 
      following treatment with NF-kappaB inhibitor. Furthermore, ANGPTL2-induced IL-6 
      upregulated the MCP-1 expression in the FJ synoviocytes. CONCLUSIONS: Mechanical 
      stress-induced ANGPTL2 promotes chronic inflammation in the FJ synovium by 
      activating IL-6 secretion, leading to FJ degeneration and subsequent LSS.
FAU - Sugimoto, Kazuki
AU  - Sugimoto K
AD  - Department of Orthopaedics, Graduate School of Medical Science, Kumamoto 
      University, Kumamoto, Japan.
FAU - Nakamura, Takayuki
AU  - Nakamura T
AD  - Department of Orthopaedics, Graduate School of Medical Science, Kumamoto 
      University, Kumamoto, Japan.
FAU - Tokunaga, Takuya
AU  - Tokunaga T
AD  - Department of Orthopaedics, Graduate School of Medical Science, Kumamoto 
      University, Kumamoto, Japan.
FAU - Uehara, Yusuke
AU  - Uehara Y
AD  - Department of Orthopaedics, Graduate School of Medical Science, Kumamoto 
      University, Kumamoto, Japan.
FAU - Okada, Tatsuya
AU  - Okada T
AD  - Department of Orthopaedics, Graduate School of Medical Science, Kumamoto 
      University, Kumamoto, Japan.
FAU - Taniwaki, Takuya
AU  - Taniwaki T
AD  - Department of Orthopaedics, Graduate School of Medical Science, Kumamoto 
      University, Kumamoto, Japan.
FAU - Fujimoto, Toru
AU  - Fujimoto T
AD  - Department of Orthopaedics, Graduate School of Medical Science, Kumamoto 
      University, Kumamoto, Japan.
FAU - Oike, Yuichi
AU  - Oike Y
AD  - Department of Molecular Genetics, Graduate School of Medical Science, Kumamoto 
      University, Kumamoto, Japan.
FAU - Nakamura, Eiichi
AU  - Nakamura E
AD  - Department of Orthopaedics, Graduate School of Medical Science, Kumamoto 
      University, Kumamoto, Japan.
LA  - eng
PT  - Journal Article
DEP - 20190129
PL  - Korea (South)
TA  - Asian Spine J
JT  - Asian spine journal
JID - 101314177
PMC - PMC6547404
OTO - NOTNLM
OT  - Angiopoietin-like protein 2
OT  - Facet joint
OT  - Interleukin-6
OT  - Lumbar spinal stenosis
OT  - Synoviocytes
COIS- No potential conflict of interest relevant to this article was reported.
EDAT- 2019/01/29 06:00
MHDA- 2019/01/29 06:01
PMCR- 2019/06/01
CRDT- 2019/01/29 06:00
PHST- 2018/07/17 00:00 [received]
PHST- 2018/09/11 00:00 [accepted]
PHST- 2019/01/29 06:00 [pubmed]
PHST- 2019/01/29 06:01 [medline]
PHST- 2019/01/29 06:00 [entrez]
PHST- 2019/06/01 00:00 [pmc-release]
AID - asj.2018.0178 [pii]
AID - asj-2018-0178 [pii]
AID - 10.31616/asj.2018.0178 [doi]
PST - ppublish
SO  - Asian Spine J. 2019 Jun;13(3):368-376. doi: 10.31616/asj.2018.0178. Epub 2019 Jan 
      29.