PMID- 31772145
OWN - NLM
STAT- MEDLINE
DCOM- 20200929
LR  - 20200929
IS  - 1945-4589 (Electronic)
IS  - 1945-4589 (Linking)
VI  - 11
IP  - 22
DP  - 2019 Nov 26
TI  - Melatonin modulates IL-1beta-induced extracellular matrix remodeling in human 
      nucleus pulposus cells and attenuates rat intervertebral disc degeneration and 
      inflammation.
PG  - 10499-10512
LID - 10.18632/aging.102472 [doi]
AB  - The inflammatory-associated factors interleukin-1beta (IL-1beta), interleukin-6 (IL-6) 
      and tumor necrosis factor-alpha (TNF-alpha) are widely reported to be associated with 
      intervertebral disc (IVD) degeneration (IVDD). N-acetyl-5-methoxytryptamine 
      (melatonin) is a natural hormone secreted by the pineal gland which has been 
      shown to participate in several physiological and pathological progresses, such 
      as aging, anti-inflammation, anti-apoptosis and autophagy regulation. However, 
      the effects of melatonin on IVD remain unclear. In the present study, we treated 
      human nucleus pulposus cells (NPCs) with melatonin and discovered that melatonin 
      could modulate extracellular matrix (ECM) remodeling induced by IL-1beta by 
      enhancing collagen II and aggrecan expression levels and by downregulating matrix 
      metalloproteinase-3 (MMP-3) levels. These findings were verified by western blot 
      and immunofluorescence assays. Intraperitoneal injection of melatonin mitigated 
      IVDD in the rat tail puncture model. X-ray and magnetic resonance imaging (MRI), 
      as well as hematoxylin-eosin (H&E), Safranine O-Green, Alcian blue and Celium red 
      staining methods were adopted to evaluate IVDD grades, the structural integrity 
      of nucleus pulposus (NP) and annulus fibrosus (AF) and the damage and 
      calcification of the cartilage endplate. Melatonin reduced inflammatory cell 
      aggregation and the release of the inflammatory factors IL-1beta, IL-6, TNF-alpha as 
      determined by immunohistochemistry. In conclusion, the present study demonstrated 
      that melatonin could modulate ECM remodeling by IL-1beta in vitro and attenuate the 
      IVDD and induction of inflammation in a rat tail puncture model in vivo. The data 
      demonstrated that melatonin may contribute to the restoration processs of IVD 
      following damage and may be used as a potential novel therapy for IVDD.
FAU - Zhang, Yan
AU  - Zhang Y
AD  - Department of Spinal Surgery, Shanghai East Hospital, Tongji University, School 
      of Medicine, Shanghai 200120, China.
FAU - He, Fan
AU  - He F
AD  - Department of Spinal Surgery, Shanghai East Hospital, Tongji University, School 
      of Medicine, Shanghai 200120, China.
FAU - Chen, Zhi
AU  - Chen Z
AD  - Department of Spine Surgery, Renji Hospital, School of Medicine, Shanghai Jiao 
      Tong University, Shanghai 200127, China.
FAU - Su, Qihang
AU  - Su Q
AD  - Department of Spinal Surgery, Shanghai East Hospital, Tongji University, School 
      of Medicine, Shanghai 200120, China.
FAU - Yan, Meijun
AU  - Yan M
AD  - Department of Spinal Surgery, Shanghai East Hospital, Tongji University, School 
      of Medicine, Shanghai 200120, China.
FAU - Zhang, Qiang
AU  - Zhang Q
AD  - Department of Spinal Surgery, Shanghai East Hospital, Tongji University, School 
      of Medicine, Shanghai 200120, China.
FAU - Tan, Jun
AU  - Tan J
AD  - Department of Spinal Surgery, Shanghai East Hospital, Tongji University, School 
      of Medicine, Shanghai 200120, China.
FAU - Qian, Lie
AU  - Qian L
AD  - Department of Spine Surgery, Renji Hospital, School of Medicine, Shanghai Jiao 
      Tong University, Shanghai 200127, China.
FAU - Han, Yingchao
AU  - Han Y
AD  - Department of Spine Surgery, Renji Hospital, School of Medicine, Shanghai Jiao 
      Tong University, Shanghai 200127, China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20191126
PL  - United States
TA  - Aging (Albany NY)
JT  - Aging
JID - 101508617
RN  - 0 (Interleukin-1beta)
RN  - JL5DK93RCL (Melatonin)
SB  - IM
MH  - Animals
MH  - Extracellular Matrix/*drug effects/metabolism/pathology
MH  - Female
MH  - Humans
MH  - Inflammation/metabolism
MH  - Interleukin-1beta/drug effects/*metabolism
MH  - *Intervertebral Disc Degeneration/metabolism/pathology
MH  - Melatonin/*pharmacology
MH  - Nucleus Pulposus/*drug effects/pathology
MH  - Rats
MH  - Rats, Sprague-Dawley
PMC - PMC6914432
OTO - NOTNLM
OT  - inflammation
OT  - intervertebral disc degeneration
OT  - melatonin
OT  - nucleus pulposus cells
COIS- CONFLICTS OF INTEREST: The authors declare no conflicts of interests.
EDAT- 2019/11/28 06:00
MHDA- 2020/09/30 06:00
PMCR- 2019/11/30
CRDT- 2019/11/28 06:00
PHST- 2019/08/02 00:00 [received]
PHST- 2019/11/06 00:00 [accepted]
PHST- 2019/11/28 06:00 [pubmed]
PHST- 2020/09/30 06:00 [medline]
PHST- 2019/11/28 06:00 [entrez]
PHST- 2019/11/30 00:00 [pmc-release]
AID - 102472 [pii]
AID - 10.18632/aging.102472 [doi]
PST - ppublish
SO  - Aging (Albany NY). 2019 Nov 26;11(22):10499-10512. doi: 10.18632/aging.102472. 
      Epub 2019 Nov 26.