PMID- 34178129
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20210629
IS  - 1792-0981 (Print)
IS  - 1792-1015 (Electronic)
IS  - 1792-0981 (Linking)
VI  - 22
IP  - 2
DP  - 2021 Aug
TI  - Lentivirus-mediated transfer of gene encoding fibroblast growth factor-18 
      inhibits intervertebral disc degeneration.
PG  - 856
LID - 10.3892/etm.2021.10288 [doi]
LID - 856
AB  - Fibroblast growth factor 18 (FGF-18) is a well-characterized anabolic growth 
      factor involved in cartilage homeostasis. However, the effect of FGF-18 on 
      intervertebral disc (IVD) degeneration has not been investigated. The present 
      study aimed to investigate the role of FGF-18 in the process of rabbit IVD 
      degeneration. In vitro, primary nucleus pulposus cells (NPs) were cultured and 
      transfected with a lentivirus. Tert-butyl hydroperoxide (TBHP) was used to induce 
      apoptosis in NPs on the second passage, while overexpression of FGF-18 in NPs 
      attenuated TBHP-induced apoptosis. A rabbit annular puncture model was generated 
      to induce IVD degeneration in vivo. The discs were injected with an 
      FGF-18-overexpression lentivirus or a negative control lentivirus. In the sham 
      group, the discs were exposed and not punctured. Disc degeneration was evaluated 
      using H&E staining and a histological grading system. Reverse 
      transcription-quantitative PCR was used to detect the expression of the 
      extracellular matrix-degrading enzymes matrix metalloproteinase-3 (MMP-3) and A 
      disintegrin and metalloproteinase with thrombospondin motifs 5 (ADAMTS-5). 
      Nucleus pulposus apoptosis was detected via western blotting, immunohistochemical 
      methods and TUNEL staining. Histologic examination showed that disc degeneration 
      was attenuated after FGF-18 overexpression treatment. At 8 weeks after surgery, 
      the expression of MMP-3 and ADAMTS-5 in the annular puncture groups was higher 
      compared with in the sham group. FGF-18 treatment inhibited the expression of 
      MMP-3 and ADAMTS-5 at the mRNA level. Western blot assays indicated that the 
      expression level of Bax was significantly reduced in the FGF-18 groups, and that 
      the expression level of Bcl-2 was significantly increased compared with those in 
      the control group. Moreover, immunohistochemical analysis indicated that the 
      FGF-18 group exhibited a lower percentage of cleaved caspase 3-positive NPs. 
      Quantification of the TUNEL staining demonstrated that the FGF-18 group had fewer 
      apoptotic NPs than the control group. These findings indicated that FGF-18 could 
      delay IVD degeneration by inhibiting the apoptosis of NPs and the expression of 
      matrix-degrading enzymes.
CI  - Copyright: (c) Lu et al.
FAU - Lu, Sheng
AU  - Lu S
AD  - Department of Spine Surgery, The First Affiliated Hospital of Wenzhou Medical 
      University, Wenzhou, Zhejiang 325000, P.R. China.
FAU - Lin, Chao-Wei
AU  - Lin CW
AD  - Department of Spine Surgery, The First Affiliated Hospital of Wenzhou Medical 
      University, Wenzhou, Zhejiang 325000, P.R. China.
LA  - eng
PT  - Journal Article
DEP - 20210609
PL  - Greece
TA  - Exp Ther Med
JT  - Experimental and therapeutic medicine
JID - 101531947
PMC - PMC8220657
OTO - NOTNLM
OT  - apoptosis
OT  - extracellular matrix-degrading enzyme
OT  - fibroblast growth factor 18
OT  - intervertebral disc degeneration
OT  - lentivirus
COIS- The authors declare that they have no competing interests.
EDAT- 2021/06/29 06:00
MHDA- 2021/06/29 06:01
PMCR- 2021/06/09
CRDT- 2021/06/28 05:57
PHST- 2020/09/17 00:00 [received]
PHST- 2021/04/23 00:00 [accepted]
PHST- 2021/06/28 05:57 [entrez]
PHST- 2021/06/29 06:00 [pubmed]
PHST- 2021/06/29 06:01 [medline]
PHST- 2021/06/09 00:00 [pmc-release]
AID - ETM-0-0-10288 [pii]
AID - 10.3892/etm.2021.10288 [doi]
PST - ppublish
SO  - Exp Ther Med. 2021 Aug;22(2):856. doi: 10.3892/etm.2021.10288. Epub 2021 Jun 9.