PMID- 31800975
OWN - NLM
STAT- MEDLINE
DCOM- 20210728
LR  - 20210728
IS  - 1523-4681 (Electronic)
IS  - 0884-0431 (Print)
IS  - 0884-0431 (Linking)
VI  - 35
IP  - 4
DP  - 2020 Apr
TI  - Differential Effect of Long-Term Systemic Exposure of TNFalpha on Health of the 
      Annulus Fibrosus and Nucleus Pulposus of the Intervertebral Disc.
PG  - 725-737
LID - 10.1002/jbmr.3931 [doi]
AB  - The inflammatory cytokine tumor necrosis factor alpha (TNFalpha) is considered to 
      play a key role in the pathogenesis of intervertebral disc disease. To evaluate 
      the importance of this cytokine we examined the inflammatory environment and 
      spinal phenotype of 9-month-old human TNFalpha overexpressing transgenic (hTNFalpha-TG) 
      mice. The mice evidenced increased circulating levels of interleukin-1beta (IL-1beta), 
      IL-2, keratinocyte chemoattractant/human growth-regulated oncogene (KC/GRO), and 
      monocyte chemoattractant protein-1 (MCP-1) along with thinning of the cortical 
      and trabecular vertebral bone. Surprisingly, although the nucleus pulposus (NP) 
      of these mice was intact and healthy, the caudal annulus fibrosus (AF) evidenced 
      robust cell death and immune cell infiltration. Despite these differences, there 
      were no obvious alterations in the collagen or aggrecan content in the NP and AF. 
      However, there was a reduction in cartilage oligomeric matrix protein (COMP), 
      suggesting destabilization of the AF matrix. Microarray analysis of the NP from 
      hTNFalpha-TG mice cells revealed minimal changes in global gene expression. These 
      findings lend support to the notion that NP tissue is isolated from systemic 
      inflammation. In contrast, the severe AF phenotype suggests that systemic 
      inflammation interferes with AF health, predisposing discs to herniation as 
      opposed to directly causing NP degeneration. (c) 2020 American Society for Bone and 
      Mineral Research.
CI  - (c) 2020 American Society for Bone and Mineral Research.
FAU - Gorth, Deborah J
AU  - Gorth DJ
AD  - Department of Orthopaedic Surgery and Graduate Program in Cell Biology and 
      Regenerative Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, 
      USA.
FAU - Ottone, Olivia K
AU  - Ottone OK
AD  - Department of Orthopaedic Surgery and Graduate Program in Cell Biology and 
      Regenerative Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, 
      USA.
FAU - Shapiro, Irving M
AU  - Shapiro IM
AD  - Department of Orthopaedic Surgery and Graduate Program in Cell Biology and 
      Regenerative Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, 
      USA.
FAU - Risbud, Makarand V
AU  - Risbud MV
AUID- ORCID: 0000-0003-3913-0649
AD  - Department of Orthopaedic Surgery and Graduate Program in Cell Biology and 
      Regenerative Medicine, Thomas Jefferson University, Philadelphia, Pennsylvania, 
      USA.
LA  - eng
GR  - R01 AR064733/AR/NIAMS NIH HHS/United States
GR  - F30 AR071256/AR/NIAMS NIH HHS/United States
GR  - T32 AR052273/AR/NIAMS NIH HHS/United States
GR  - R01 AR074813/AR/NIAMS NIH HHS/United States
GR  - R01 AR055655/AR/NIAMS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
DEP - 20200106
PL  - England
TA  - J Bone Miner Res
JT  - Journal of bone and mineral research : the official journal of the American 
      Society for Bone and Mineral Research
JID - 8610640
SB  - IM
MH  - Animals
MH  - *Annulus Fibrosus
MH  - *Intervertebral Disc
MH  - *Intervertebral Disc Degeneration
MH  - *Intervertebral Disc Displacement
MH  - Mice
MH  - *Nucleus Pulposus
PMC - PMC7145745
MID - NIHMS1065493
OTO - NOTNLM
OT  - COLLAGEN
OT  - CYTOKINES
OT  - GENETIC ANIMAL MODELS
COIS- Conflicts of Interest: None for all authors.
EDAT- 2019/12/05 06:00
MHDA- 2021/07/29 06:00
PMCR- 2021/04/01
CRDT- 2019/12/05 06:00
PHST- 2019/06/02 00:00 [received]
PHST- 2019/11/07 00:00 [revised]
PHST- 2019/11/22 00:00 [accepted]
PHST- 2019/12/05 06:00 [pubmed]
PHST- 2021/07/29 06:00 [medline]
PHST- 2019/12/05 06:00 [entrez]
PHST- 2021/04/01 00:00 [pmc-release]
AID - 10.1002/jbmr.3931 [doi]
PST - ppublish
SO  - J Bone Miner Res. 2020 Apr;35(4):725-737. doi: 10.1002/jbmr.3931. Epub 2020 Jan 
      6.