PMID- 32723833
OWN - NLM
STAT- MEDLINE
DCOM- 20210610
LR  - 20210610
IS  - 2056-5933 (Electronic)
IS  - 2056-5933 (Linking)
VI  - 6
IP  - 2
DP  - 2020 Jul
TI  - Dual neutralisation of IL-17F and IL-17A with bimekizumab blocks 
      inflammation-driven osteogenic differentiation of human periosteal cells.
LID - 10.1136/rmdopen-2020-001306 [doi]
LID - e001306
AB  - OBJECTIVES: Interleukin (IL)-17 signalling has been shown to be a key regulator 
      of disease in ankylosing spondylitis (AS) with several IL-17 blockers currently 
      clinically approved. Despite this, the role of IL-17 in bone pathology is poorly 
      understood. This study aimed to investigate IL-17 signalling in the context of 
      pathological bone formation. METHODS: A biomimetic human periosteum-derived cell 
      (hPDC) model of osteogenic differentiation was used in combination with 
      recombinant IL-17 cytokines, T-cell supernatants or serum from patients with AS. 
      IL-17A, IL-17F and bimekizumab monoclonal antibodies were used to block IL-17 
      cytokine action. RESULTS: Recombinant IL-17A and IL-17F are pro-osteogenic with 
      respect to hPDC differentiation. T helper 17 or gammadelta-T cell supernatants also 
      potently stimulated in vitro bone formation, which was blocked deeper by dual 
      inhibition of IL-17A and IL-17F than by neutralisation of IL-17A or IL-17F 
      individually. Osteogenic blockade may be due to an increase in expression of the 
      Wnt antagonist DKK1. Interestingly, osteocommitment was also induced by serum 
      obtained from patients with AS, which was also abrogated by dual neutralisation 
      of IL-17A and IL-17F. CONCLUSIONS: These data show for the first time that IL-17A 
      and IL-17F enhance in vitro osteogenic differentiation and bone formation from 
      hPDCs, inhibition of which may offer an attractive therapeutic strategy to 
      prevent pathological bone formation.
CI  - (c) Author(s) (or their employer(s)) 2020. Re-use permitted under CC BY-NC. No 
      commercial re-use. See rights and permissions. Published by BMJ.
FAU - Shah, Mittal
AU  - Shah M
AD  - UCB Pharma, Slough, UK.
AD  - Division of Surgery and Interventional Science, University College London, 
      London, UK.
FAU - Maroof, Asher
AU  - Maroof A
AD  - UCB Pharma, Slough, UK.
FAU - Gikas, Panos
AU  - Gikas P
AD  - Royal National Orthopaedic Hospital Stanmore, Stanmore, UK.
FAU - Mittal, Gayatri
AU  - Mittal G
AD  - Royal National Orthopaedic Hospital Stanmore, Stanmore, UK.
FAU - Keen, Richard
AU  - Keen R
AD  - Royal National Orthopaedic Hospital Stanmore, Stanmore, UK.
FAU - Baeten, Dominique
AU  - Baeten D
AD  - UCB Pharma, Slough, UK.
FAU - Shaw, Stevan
AU  - Shaw S
AD  - UCB Pharma, Slough, UK.
FAU - Roberts, Scott J
AU  - Roberts SJ
AUID- ORCID: 0000-0003-3974-8895
AD  - UCB Pharma, Slough, UK scott.roberts@ucl.ac.uk.
AD  - Division of Surgery and Interventional Science, University College London, 
      London, UK.
AD  - Department of Comparative Biomedical Sciences, Royal Veterinary College, London, 
      UK.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - RMD Open
JT  - RMD open
JID - 101662038
RN  - 0 (Antibodies, Monoclonal, Humanized)
RN  - 0 (Antibodies, Neutralizing)
RN  - 0 (Cytokines)
RN  - 0 (IL17A protein, human)
RN  - 0 (IL17F protein, human)
RN  - 0 (IL17RA protein, human)
RN  - 0 (IL17RC protein, human)
RN  - 0 (Interleukin-17)
RN  - 0 (Receptors, Antigen, T-Cell, gamma-delta)
RN  - 0 (Receptors, Interleukin)
RN  - 0 (Receptors, Interleukin-17)
RN  - 09495UIM6V (bimekizumab)
SB  - IM
MH  - Antibodies, Monoclonal, Humanized/*pharmacology
MH  - Antibodies, Neutralizing/pharmacology
MH  - Bone Matrix/metabolism
MH  - Calcification, Physiologic/drug effects/genetics
MH  - Cell Differentiation/*drug effects
MH  - Cytokines/genetics/metabolism
MH  - Humans
MH  - Interleukin-17/*antagonists & inhibitors/metabolism
MH  - Osteogenesis/*drug effects
MH  - Periosteum/*cytology
MH  - Receptors, Antigen, T-Cell, gamma-delta/metabolism
MH  - Receptors, Interleukin/genetics/metabolism
MH  - Receptors, Interleukin-17/genetics/metabolism
MH  - Th17 Cells/immunology/metabolism
PMC - PMC7722278
OTO - NOTNLM
OT  - Ankylosing Spondylitis
OT  - Cytokines
OT  - Inflammation
OT  - TCells
COIS- Competing interests: MS, AM, SS and DB are employees of UCB Pharma. PG has 
      received honoraria from Medacta International. RK has received honoraria from 
      Kyowa Kirin, Amgen and Clementia Pharmaceuticals, and consulting fees from Kyowa 
      Kirin and Clementia Pharmaceuticals. SR is a former employee of UCB Pharma and 
      has received consulting fees from Angitia Biopharmaceuticals.
EDAT- 2020/07/30 06:00
MHDA- 2021/06/11 06:00
PMCR- 2020/07/28
CRDT- 2020/07/30 06:00
PHST- 2020/05/05 00:00 [received]
PHST- 2020/06/25 00:00 [revised]
PHST- 2020/06/25 00:00 [accepted]
PHST- 2020/07/30 06:00 [entrez]
PHST- 2020/07/30 06:00 [pubmed]
PHST- 2021/06/11 06:00 [medline]
PHST- 2020/07/28 00:00 [pmc-release]
AID - rmdopen-2020-001306 [pii]
AID - 10.1136/rmdopen-2020-001306 [doi]
PST - ppublish
SO  - RMD Open. 2020 Jul;6(2):e001306. doi: 10.1136/rmdopen-2020-001306.