PMID- 28576140
OWN - NLM
STAT- MEDLINE
DCOM- 20180102
LR  - 20181113
IS  - 1478-6362 (Electronic)
IS  - 1478-6354 (Print)
IS  - 1478-6354 (Linking)
VI  - 19
IP  - 1
DP  - 2017 Jun 2
TI  - RANK/RANKL/OPG system in the intervertebral disc.
PG  - 121
LID - 10.1186/s13075-017-1332-y [doi]
LID - 121
AB  - BACKGROUND: The receptor activator of NF-kappaB ligand (RANKL), a member of the TNF 
      ligand superfamily, is known to regulate bone metabolism. The expression of each 
      component of the RANK/RANKL/osteoprotegerin (OPG) system in the intervertebral 
      disc (IVD) has not been examined in detail. The purposes of this study were to 
      examine the expression of the RANK/RANKL/OPG system and to evaluate the function 
      of RANKL in the matrix metabolism of the rat IVD. METHODS: Sprague-Dawley, 
      12-week-old, male rats were used in this study. Anulus fibrosus (AF), nucleus 
      pulposus (NP) and cartilaginous endplate (CEP) cells isolated from dissected 
      thoracolumbar discs were monolayer-cultured. RANK/RANKL/OPG expression in rat 
      IVDs was examined using real-time polymerase chain reaction (PCR) and 
      immunohistochemical analysis (cultured cells and IVD tissues). To examine the 
      effect of interleukin-1beta (IL-1beta) stimulation on the mRNA levels of RANK, RANKL 
      and OPG, the cells were cultured with or without recombinant human IL-1beta 
      (rhIL-1beta). To evaluate the effect of RANKL on the mRNA expression of catabolic 
      factors (IL-1beta, matrix metalloproteinase-3 (MMP-3) and MMP-13), the cells were 
      cultured with RANKL in the presence or absence of rhIL-1beta. The 
      immunohistochemical expression of this system was also evaluated using human IVD 
      tissues with different grades of degeneration. RESULTS: mRNA expression levels of 
      RANK, RANKL, and OPG were clearly identified in AF, NP and CEP cells. 
      Immunoreactivity to RANK, RANKL and OPG was distributed in the cell membranes 
      and/or cytoplasm of the three types of cells. The mRNA level of RANKL was 
      significantly upregulated by treatment with rhIL-1beta of the three types of cells. 
      Treatment with RANKL without rhIL-1beta did not induce significant effects on the 
      mRNA expression of catabolic factors by AF, NP and CEP cells. However, the 
      expression was significantly upregulated by stimulation with RANKL in the 
      presence of rhIL-1beta. There was a general trend for more RANK/RANKL/OPG-positive 
      cells in human IVD tissues in an advanced stage of degeneration compared to an 
      early stage. CONCLUSIONS: Our study showed the possibility that the 
      RANK/RANKL/OPG system may play a part in the process of intervertebral disc 
      degeneration.
FAU - Takegami, Norihiko
AU  - Takegami N
AD  - Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, 
      2-174 Edobashi, Tsu City, Mie, 514-8507, Japan.
FAU - Akeda, Koji
AU  - Akeda K
AD  - Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, 
      2-174 Edobashi, Tsu City, Mie, 514-8507, Japan. k_akeda@clin.medic.mie-u.ac.jp.
FAU - Yamada, Junichi
AU  - Yamada J
AD  - Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, 
      2-174 Edobashi, Tsu City, Mie, 514-8507, Japan.
FAU - Sano, Tomohiko
AU  - Sano T
AD  - Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, 
      2-174 Edobashi, Tsu City, Mie, 514-8507, Japan.
FAU - Murata, Koichiro
AU  - Murata K
AD  - Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, 
      2-174 Edobashi, Tsu City, Mie, 514-8507, Japan.
FAU - Huang, Jenny
AU  - Huang J
AD  - Department of Orthopaedic Surgery, University of California, San Diego, 9500 
      Gilman Dr, La Jolla, 92093-0863, USA.
FAU - Masuda, Koichi
AU  - Masuda K
AD  - Department of Orthopaedic Surgery, University of California, San Diego, 9500 
      Gilman Dr, La Jolla, 92093-0863, USA.
FAU - Sudo, Akihiro
AU  - Sudo A
AD  - Department of Orthopaedic Surgery, Mie University Graduate School of Medicine, 
      2-174 Edobashi, Tsu City, Mie, 514-8507, Japan.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170602
PL  - England
TA  - Arthritis Res Ther
JT  - Arthritis research & therapy
JID - 101154438
RN  - 0 (Osteoprotegerin)
RN  - 0 (RANK Ligand)
RN  - 0 (Receptor Activator of Nuclear Factor-kappa B)
SB  - IM
MH  - Animals
MH  - Humans
MH  - Intervertebral Disc/*metabolism/pathology
MH  - Intervertebral Disc Degeneration/*metabolism
MH  - Male
MH  - Osteoprotegerin/*metabolism
MH  - RANK Ligand/*metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor Activator of Nuclear Factor-kappa B/*metabolism
MH  - Signal Transduction/physiology
PMC - PMC5457592
OTO - NOTNLM
OT  - Cartilaginous endplate
OT  - Intervertebral disc
OT  - Osteoprotegerin
OT  - Proinflammatory cytokine
OT  - Receptor activator of nuclear factor kappa B
OT  - Receptor activator of nuclear factor kappa B ligand
EDAT- 2017/06/04 06:00
MHDA- 2018/01/03 06:00
PMCR- 2017/06/02
CRDT- 2017/06/04 06:00
PHST- 2016/11/29 00:00 [received]
PHST- 2017/05/15 00:00 [accepted]
PHST- 2017/06/04 06:00 [entrez]
PHST- 2017/06/04 06:00 [pubmed]
PHST- 2018/01/03 06:00 [medline]
PHST- 2017/06/02 00:00 [pmc-release]
AID - 10.1186/s13075-017-1332-y [pii]
AID - 1332 [pii]
AID - 10.1186/s13075-017-1332-y [doi]
PST - epublish
SO  - Arthritis Res Ther. 2017 Jun 2;19(1):121. doi: 10.1186/s13075-017-1332-y.