PMID- 24928317
OWN - NLM
STAT- MEDLINE
DCOM- 20150511
LR  - 20220311
IS  - 1522-9653 (Electronic)
IS  - 1063-4584 (Linking)
VI  - 22
IP  - 8
DP  - 2014 Aug
TI  - Treatment efficacy of adipose-derived stem cells in experimental osteoarthritis 
      is driven by high synovial activation and reflected by S100A8/A9 serum levels.
PG  - 1158-66
LID - S1063-4584(14)01101-7 [pii]
LID - 10.1016/j.joca.2014.05.022 [doi]
AB  - OBJECTIVE: Synovitis is evident in a substantial subpopulation of patients with 
      osteoarthritis (OA) and is associated with development of pathophysiology. 
      Recently we have shown that adipose-derived stem cells (ASC) inhibit joint 
      destruction in collagenase-induced experimental OA (CIOA). In the current study 
      we explored the role of synovitis and alarmins S100A8/A9 in the immunomodulatory 
      capacity of ASCs in experimental OA. METHOD: CIOA, characterized by synovitis, 
      and surgical DMM (destabilization of medial meniscus) OA were treated locally 
      with ASCs. Synovial activation, cartilage damage and osteophyte size were 
      measured on histological sections. Cytokines in synovial washouts and serum were 
      determined using Luminex or enzyme-linked immunosorbent assay (S100A8/A9), mRNA 
      levels with reverse-transcriptase (RT)-qPCR. RESULTS: Local administration of 
      ASCs at various time-points (days 7 or 14) after DMM induction had no effect on 
      OA pathology. At day 7 of CIOA, already 6 h after ASC injection mRNA expression 
      of pro-inflammatory mediators S100A8/A9, interleukin-1beta (IL-1beta) and KC was 
      down-regulated in the synovium. IL-1beta protein, although low, was down-regulated 
      by ASC-treatment of CIOA. S100A8/A9 protein levels were very high at 6 and 48 h 
      and were decreased by ASC-treatment. The protective action of ASC treatment in 
      CIOA was only found when high synovial inflammation was present at the time of 
      deposition which was reflected by high serum S100A8/A9 levels. Finally, 
      successful treatment resulted in significantly lower levels of serum S100A8/A9. 
      CONCLUSION: Our study indicates that synovial activation rapidly drives 
      anti-inflammatory and protective effects of intra-articularly deposited ASCs in 
      experimental OA which is reflected by decreased S100A8/A9 levels.
CI  - Copyright (c) 2014 Osteoarthritis Research Society International. Published by 
      Elsevier Ltd. All rights reserved.
FAU - Schelbergen, R F
AU  - Schelbergen RF
AD  - Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The 
      Netherlands. Electronic address: Rik.Schelbergen@radboudumc.nl.
FAU - van Dalen, S
AU  - van Dalen S
AD  - Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The 
      Netherlands.
FAU - ter Huurne, M
AU  - ter Huurne M
AD  - Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The 
      Netherlands.
FAU - Roth, J
AU  - Roth J
AD  - Institute of Immunology, University of Munster, Germany.
FAU - Vogl, T
AU  - Vogl T
AD  - Institute of Immunology, University of Munster, Germany.
FAU - Noel, D
AU  - Noel D
AD  - Inserm U844, Hopital Saint-Eloi, Montpellier, France.
FAU - Jorgensen, C
AU  - Jorgensen C
AD  - Inserm U844, Hopital Saint-Eloi, Montpellier, France.
FAU - van den Berg, W B
AU  - van den Berg WB
AD  - Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The 
      Netherlands.
FAU - van de Loo, F A
AU  - van de Loo FA
AD  - Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The 
      Netherlands.
FAU - Blom, A B
AU  - Blom AB
AD  - Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The 
      Netherlands.
FAU - van Lent, P L E M
AU  - van Lent PL
AD  - Experimental Rheumatology, Radboud University Medical Center, Nijmegen, The 
      Netherlands. Electronic address: Peter.vanLent@radboudumc.nl.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140610
PL  - England
TA  - Osteoarthritis Cartilage
JT  - Osteoarthritis and cartilage
JID - 9305697
RN  - 0 (Calgranulin A)
RN  - 0 (Calgranulin B)
RN  - 0 (IL1B protein, mouse)
RN  - 0 (Interleukin-1beta)
RN  - 0 (RNA, Messenger)
RN  - 0 (S100A9 protein, mouse)
RN  - 0 (S100a8 protein, mouse)
RN  - EC 3.4.24.- (Collagenases)
SB  - IM
MH  - Adipose Tissue/cytology
MH  - Animals
MH  - Arthritis, Experimental/*therapy
MH  - Calgranulin A/*blood/genetics
MH  - Calgranulin B/*blood/genetics
MH  - Cartilage, Articular/metabolism
MH  - Collagenases/toxicity
MH  - Disease Models, Animal
MH  - Interleukin-1beta/genetics/metabolism
MH  - Menisci, Tibial/*surgery
MH  - Mice
MH  - Osteoarthritis, Knee/metabolism/*therapy
MH  - RNA, Messenger/*genetics
MH  - Reverse Transcriptase Polymerase Chain Reaction
MH  - Stem Cell Transplantation/*methods
MH  - Stem Cells/cytology
MH  - Synovial Membrane/*metabolism
MH  - Synovitis/metabolism/therapy
OTO - NOTNLM
OT  - Adipose stem cells
OT  - Animal models
OT  - Experimental OA
OT  - S100
OT  - Synovitis
EDAT- 2014/06/15 06:00
MHDA- 2015/05/12 06:00
CRDT- 2014/06/15 06:00
PHST- 2014/04/08 00:00 [received]
PHST- 2014/05/23 00:00 [revised]
PHST- 2014/05/28 00:00 [accepted]
PHST- 2014/06/15 06:00 [entrez]
PHST- 2014/06/15 06:00 [pubmed]
PHST- 2015/05/12 06:00 [medline]
AID - S1063-4584(14)01101-7 [pii]
AID - 10.1016/j.joca.2014.05.022 [doi]
PST - ppublish
SO  - Osteoarthritis Cartilage. 2014 Aug;22(8):1158-66. doi: 
      10.1016/j.joca.2014.05.022. Epub 2014 Jun 10.