PMID- 26801240
OWN - NLM
STAT- MEDLINE
DCOM- 20161006
LR  - 20181113
IS  - 1478-6362 (Electronic)
IS  - 1478-6354 (Print)
IS  - 1478-6354 (Linking)
VI  - 18
DP  - 2016 Jan 23
TI  - Anti-RANKL treatment inhibits erosive joint destruction and lowers inflammation 
      but has no effect on bone formation in the delayed-type hypersensitivity 
      arthritis (DTHA) model.
PG  - 28
LID - 10.1186/s13075-016-0931-3 [doi]
LID - 28
AB  - BACKGROUND: The aims of the present study were to determine the relationship 
      between bone destruction and bone formation in the delayed-type hypersensitivity 
      arthritis (DTHA) model and to evaluate the effect of receptor activator of 
      nuclear factor kappaB ligand (RANKL) blockade on severity of arthritis, bone 
      destruction, and bone formation. METHODS: DTHA was induced in C57BL/6 mice. 
      Inflammation, erosive joint damage, and new bone formation were 
      semiquantitatively scored by histology. Osteoclast activity was assessed in vivo, 
      and messenger RNA (mRNA) expression of mediators of bone destruction and bone 
      formation were analyzed by mRNA deep sequencing. Serum concentrations of 
      tartrate-resistant acid phosphatase 5b, carboxy-terminal telopeptide I (CTX-I), 
      matrix metalloproteinase 3 (MMP3), and serum amyloid P component (SAP) were 
      determined by enzyme-linked immunosorbent assay. Anti-RANKL monoclonal antibody 
      treatment was initiated at the time of immunization. RESULTS: Bone destruction 
      (MMP3 serum levels, cathepsin B activity, and RANKL mRNA) peaked at day 3 after 
      arthritis induction, followed by a peak in cartilage destruction and bone erosion 
      on day 5 after arthritis induction. Periarticular bone formation was observed 
      from day 10. Induction of new bone formation indicated by enhanced Runx2, 
      collagen X, osteocalcin, MMP2, MMP9, and MMP13 mRNA expression was observed only 
      between days 8 and 11. Anti-RANKL treatment resulted in a modest reduction in paw 
      and ankle swelling and a reduction of serum levels of SAP, MMP3, and CTX-I. 
      Destruction of the subchondral bone was significantly reduced, while no effect on 
      bone formation was seen. CONCLUSIONS: Anti-RANKL treatment prevents joint 
      destruction but does not prevent new bone formation in the DTHA model. Thus, 
      although occurring sequentially during the course of DTHA, bone destruction and 
      bone formation are apparently not linked in this model.
FAU - Atkinson, Sara Marie
AU  - Atkinson SM
AD  - Global Research, Novo Nordisk A/S, 2760, Malov, Denmark. saii@novonordisk.com.
AD  - Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of 
      Copenhagen, 1870 Frederiksberg, C, Denmark. saii@novonordisk.com.
FAU - Bleil, Janine
AU  - Bleil J
AD  - Medizinische Klinik fur Gastroenterologie, Infektiologie und Rheumatologie, 
      Charite, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany. 
      janine.bleil@gmx.de.
FAU - Maier, Rene
AU  - Maier R
AD  - German Rheumatism Research Center, Berlin, Germany. rene.maier@drfz.de.
FAU - Kuhl, Anja A
AU  - Kuhl AA
AD  - Medizinische Klinik fur Gastroenterologie, Infektiologie und Rheumatologie, 
      Charite, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany. 
      anja.kuehl@charite.de.
FAU - Thorn, Mette
AU  - Thorn M
AD  - Bioneer, Horsholm, Denmark. mth@bioneer.dk.
FAU - Serikawa, Kyle
AU  - Serikawa K
AD  - Benaroya Research Institute, Seattle, WA, USA. kserikawa@benaroyaresearch.org.
FAU - Fox, Brian
AU  - Fox B
AD  - Immunexpress, Seattle, WA, USA. bandrewfox@gmail.com.
FAU - Kruse, Kim
AU  - Kruse K
AD  - Global Research, Novo Nordisk, Seattle, WA, USA. kimkruse911@gmail.com.
FAU - Haase, Claus
AU  - Haase C
AD  - Global Research, Novo Nordisk A/S, 2760, Malov, Denmark. csha@novonordisk.com.
FAU - Skov, Soren
AU  - Skov S
AD  - Veterinary Disease Biology, Faculty of Health and Medical Sciences, University of 
      Copenhagen, 1870 Frederiksberg, C, Denmark. sosk@sund.ku.dk.
FAU - Nansen, Anneline
AU  - Nansen A
AD  - Department of Pharmacology, Zealand Pharma, Glostrup, Denmark. 
      ana@zealandpharma.com.
FAU - Syrbe, Uta
AU  - Syrbe U
AD  - Medizinische Klinik fur Gastroenterologie, Infektiologie und Rheumatologie, 
      Charite, Campus Benjamin Franklin, Hindenburgdamm 30, 12200, Berlin, Germany. 
      uta.syrbe@charite.de.
AD  - German Rheumatism Research Center, Berlin, Germany. uta.syrbe@charite.de.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20160123
PL  - England
TA  - Arthritis Res Ther
JT  - Arthritis research & therapy
JID - 101154438
RN  - 0 (Antibodies, Monoclonal)
RN  - 0 (RANK Ligand)
RN  - 0 (Tnfsf11 protein, mouse)
SB  - IM
MH  - Animals
MH  - Antibodies, Monoclonal/pharmacology/*therapeutic use
MH  - Arthritis, Experimental/*drug therapy/metabolism/*pathology
MH  - Female
MH  - Inflammation/drug therapy/metabolism/pathology
MH  - Joints/drug effects/metabolism/*pathology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Osteogenesis/drug effects/*physiology
MH  - RANK Ligand/*antagonists & inhibitors/metabolism
MH  - Rats
PMC - PMC4724155
EDAT- 2016/01/24 06:00
MHDA- 2016/10/08 06:00
PMCR- 2016/01/23
CRDT- 2016/01/24 06:00
PHST- 2015/11/18 00:00 [received]
PHST- 2016/01/11 00:00 [accepted]
PHST- 2016/01/24 06:00 [entrez]
PHST- 2016/01/24 06:00 [pubmed]
PHST- 2016/10/08 06:00 [medline]
PHST- 2016/01/23 00:00 [pmc-release]
AID - 10.1186/s13075-016-0931-3 [pii]
AID - 931 [pii]
AID - 10.1186/s13075-016-0931-3 [doi]
PST - epublish
SO  - Arthritis Res Ther. 2016 Jan 23;18:28. doi: 10.1186/s13075-016-0931-3.