TGF-β regulates nerve growth factor expression in a mouse intervertebral disc injury model.
Intervertebral disc
Nerve growth factor
Transforming growth factor-β
Journal
BMC musculoskeletal disorders
ISSN: 1471-2474
Titre abrégé: BMC Musculoskelet Disord
Pays: England
ID NLM: 100968565
Informations de publication
Date de publication:
23 Jul 2021
23 Jul 2021
Historique:
received:
02
04
2021
accepted:
06
07
2021
entrez:
24
7
2021
pubmed:
25
7
2021
medline:
28
7
2021
Statut:
epublish
Résumé
Intervertebral disc (IVD) degeneration is a major cause of low back pain (LBP). Following disc injury, nerve growth factor (NGF) concentrations rise in IVDs, and anti-NGF therapy has been shown to attenuate LBP in humans. Increased levels of tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β) in degenerative IVDs and in in vitro studies suggest that these factors promote NGF production. However, whether these factors regulate NGF in vivo remains unclear. Thus, we studied NGF regulation in a mouse model of IVD injury. After inducing IVD injury, we examined mRNA levels of Tnfa, Tgfb, and Ngf in IVDs from control and IVD-injured mice across 7 days. To do this, we used magnetic cell separation to isolate CD11b ( +) (macrophage-rich) and CD11b (-) (IVD cell-rich) cell fractions from injured IVDs. To study the effect of TNF-α on Ngf expression, we examined Ngf expression in injured IVDs from C57BL/6 J and Tnfa-knockout (KO) mice (C57BL/6 J background). To study the effect of TGF-β on Ngf expression, C57/BL6J mice were given an intraperitoneal injection of either the TGF-β inhibitor SB431542 or DMSO solution (vehicle) one and two days before harvesting IVDs. mRNA expression of Tnfa, Tgfb, and Ngf was significantly increased in injured IVDs. Tnfa was predominantly expressed in the CD11b ( +) fraction, and Tgfb in the CD11b (-) fraction. Ngf expression was comparable between CD11b ( +) and CD11b (-) fractions, and between wild-type and Tnfa-KO mice at post-injury day (PID) 1, 3, and 7. SB431542 suppressed TGF-β-mediated Ngf expression and NGF production in vitro. Further, administration of SB431542 significantly reduced Ngf expression in IVDs such that levels were below those observed in vehicle-treated animals at PID3 and PID7. A TGF-β inhibitor reduced Ngf expression in a mouse model of IVD injury, suggesting that TGF-β may regulate NGF expression in vivo.
Sections du résumé
BACKGROUND
BACKGROUND
Intervertebral disc (IVD) degeneration is a major cause of low back pain (LBP). Following disc injury, nerve growth factor (NGF) concentrations rise in IVDs, and anti-NGF therapy has been shown to attenuate LBP in humans. Increased levels of tumor necrosis factor-α (TNF-α) and transforming growth factor-β (TGF-β) in degenerative IVDs and in in vitro studies suggest that these factors promote NGF production. However, whether these factors regulate NGF in vivo remains unclear. Thus, we studied NGF regulation in a mouse model of IVD injury.
METHODS
METHODS
After inducing IVD injury, we examined mRNA levels of Tnfa, Tgfb, and Ngf in IVDs from control and IVD-injured mice across 7 days. To do this, we used magnetic cell separation to isolate CD11b ( +) (macrophage-rich) and CD11b (-) (IVD cell-rich) cell fractions from injured IVDs. To study the effect of TNF-α on Ngf expression, we examined Ngf expression in injured IVDs from C57BL/6 J and Tnfa-knockout (KO) mice (C57BL/6 J background). To study the effect of TGF-β on Ngf expression, C57/BL6J mice were given an intraperitoneal injection of either the TGF-β inhibitor SB431542 or DMSO solution (vehicle) one and two days before harvesting IVDs.
RESULTS
RESULTS
mRNA expression of Tnfa, Tgfb, and Ngf was significantly increased in injured IVDs. Tnfa was predominantly expressed in the CD11b ( +) fraction, and Tgfb in the CD11b (-) fraction. Ngf expression was comparable between CD11b ( +) and CD11b (-) fractions, and between wild-type and Tnfa-KO mice at post-injury day (PID) 1, 3, and 7. SB431542 suppressed TGF-β-mediated Ngf expression and NGF production in vitro. Further, administration of SB431542 significantly reduced Ngf expression in IVDs such that levels were below those observed in vehicle-treated animals at PID3 and PID7.
CONCLUSION
CONCLUSIONS
A TGF-β inhibitor reduced Ngf expression in a mouse model of IVD injury, suggesting that TGF-β may regulate NGF expression in vivo.
Identifiants
pubmed: 34301215
doi: 10.1186/s12891-021-04509-w
pii: 10.1186/s12891-021-04509-w
pmc: PMC8299674
doi:
Substances chimiques
Transforming Growth Factor beta
0
Nerve Growth Factor
9061-61-4
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
634Informations de copyright
© 2021. The Author(s).
Références
Arthritis Rheum. 1992 Mar;35(3):351-5
pubmed: 1536673
Osteoarthritis Cartilage. 2019 Aug;27(8):1109-1117
pubmed: 31132405
J Orthop Res. 2019 Aug;37(8):1798-1804
pubmed: 30977543
PLoS One. 2015 Dec 02;10(12):e0143961
pubmed: 26630505
Nat Rev Rheumatol. 2021 Jan;17(1):34-46
pubmed: 33219344
J Orthop Res. 2020 Aug;38(8):1703-1709
pubmed: 31965590
Scoliosis Spinal Disord. 2017 Apr 18;12:14
pubmed: 28435906
Kidney Int. 2013 Oct;84(4):745-55
pubmed: 23636175
Expert Rev Clin Pharmacol. 2020 Jun;13(6):631-639
pubmed: 32436473
J Orthop Res. 2020 Apr;38(4):895-901
pubmed: 31721276
J Pathol. 2009 May;218(1):113-21
pubmed: 19288580
J Orthop Res. 2016 May;34(5):865-75
pubmed: 26505752
Arthritis Res Ther. 2007;9(4):R77
pubmed: 17688691
J Orthop Res. 2018 Mar 6;:
pubmed: 29508435
J Orthop Res. 2013 Aug;31(8):1276-82
pubmed: 23553925
BMC Musculoskelet Disord. 2019 May 10;20(1):204
pubmed: 31077183
Arthritis Res Ther. 2014 Jul 28;16(4):R159
pubmed: 25069717
Nat Rev Genet. 2004 Feb;5(2):101-13
pubmed: 14735121
PLoS One. 2016 Aug 02;11(8):e0160486
pubmed: 27482708
Phys Med Rehabil Clin N Am. 2014 May;25(2):305-17
pubmed: 24787335
Pain. 2019 Oct;160(10):2210-2220
pubmed: 31145219
Eur Spine J. 2006 May;15(5):588-96
pubmed: 15980999
Cytokine. 2002 Nov 7;20(3):136-9
pubmed: 12453472
Pain Manag. 2015 Sep;5(5):373-86
pubmed: 26255722
Bioessays. 1992 Apr;14(4):263-6
pubmed: 1596275
Nat Med. 2015 Jul;21(7):786-94
pubmed: 26053624
Dev Dyn. 2021 Jul;250(7):1036-1050
pubmed: 33452727
Phys Ther. 2018 May 1;98(5):434-446
pubmed: 29669088
Rheumatol Int. 1998;18(3):97-102
pubmed: 9833249
Am J Phys Med Rehabil. 2018 Mar;97(3):170-177
pubmed: 28863006
Br J Pharmacol. 1995 Aug;115(7):1265-75
pubmed: 7582555
Spine (Phila Pa 1976). 2007 Mar 15;32(6):635-42
pubmed: 17413467