Insulin-Like Growth Factor I Does Not Drive New Bone Formation in Experimental Arthritis.
BACKGROUND
Insulin like growth factor (IGF)-I can act on a variety of cells involved in cartilage and bone repair, yet IGF-I has not been studied extensively in the context of inflammatory arthritis. The objective of this study was to investigate whether IGF-I overexpression in the osteoblast lineage could lead to increased reparative or pathological bone formation in rheumatoid arthritis and/or spondyloarthritis respectively.


METHODS
Mice overexpressing IGF-I in the osteoblast lineage (Ob-IGF-I+/-) line 324-7 were studied during collagen induced arthritis and in the DBA/1 aging model for ankylosing enthesitis. Mice were scored clinically and peripheral joints were analysed histologically for the presence of hypertrophic chondrocytes and osteocalcin positive osteoblasts.


RESULTS
90-100% of the mice developed CIA with no differences between the Ob-IGF-I+/- and non-transgenic littermates. Histological analysis revealed similar levels of hypertrophic chondrocytes and osteocalcin positive osteoblasts in the ankle joints. In the DBA/1 aging model for ankylosing enthesitis 60% of the mice in both groups had a clinical score 1<. Severity was similar between both groups. Histological analysis revealed the presence of hypertrophic chondrocytes and osteocalcin positive osteoblasts in the toes in equal levels.


CONCLUSIONS
Overexpression of IGF-I in the osteoblast lineage does not contribute to an increase in repair of erosions or syndesmophyte formation in mouse models for destructive and remodeling arthritis.
Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology and Rheumatology, Academic Medical Center / University of Amsterdam, Amsterdam, The Netherlands.|Department of Experimental Immunology, Academic Medical Center / University of Amsterdam, Amsterdam, The Netherlands.
Melissa N
MN
van Tok
Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology and Rheumatology, Academic Medical Center / University of Amsterdam, Amsterdam, The Netherlands.|Department of Experimental Immunology, Academic Medical Center / University of Amsterdam, Amsterdam, The Netherlands.
Nataliya G
NG
Yeremenko
Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology and Rheumatology, Academic Medical Center / University of Amsterdam, Amsterdam, The Netherlands.|Department of Experimental Immunology, Academic Medical Center / University of Amsterdam, Amsterdam, The Netherlands.
Christine A
CA
Teitsma
Department of Medicine, Uconn Health, Farmington, CT, United States of America.
Barbara E
BE
Kream
Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology and Rheumatology, Academic Medical Center / University of Amsterdam, Amsterdam, The Netherlands.|Department of Experimental Immunology, Academic Medical Center / University of Amsterdam, Amsterdam, The Netherlands.
Véronique L
VL
Knaup
Laboratory of Tissue Homeostasis and Disease, Skeletal Biology and Engineering Research Center, KU Leuven, Leuven, Belgium.|Division of Rheumatology, University Hospitals Leuven, Leuven, Belgium.
Rik J
RJ
Lories
Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology and Rheumatology, Academic Medical Center / University of Amsterdam, Amsterdam, The Netherlands.|Department of Experimental Immunology, Academic Medical Center / University of Amsterdam, Amsterdam, The Netherlands.
Dominique L
DL
Baeten
Amsterdam Rheumatology and Immunology Center, Department of Clinical Immunology and Rheumatology, Academic Medical Center / University of Amsterdam, Amsterdam, The Netherlands.|Department of Experimental Immunology, Academic Medical Center / University of Amsterdam, Amsterdam, The Netherlands.
Leonie M
LM
van Duivenvoorde
D000818:Animals; D001169:Arthritis, Experimental / Q000235:genetics* / Q000503:physiopathology; D002356:Cartilage / Q000254:growth & development / Q000378:metabolism; D002454:Cell Differentiation / Q000235:genetics; D002460:Cell Line; D019902:Chondrocytes / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D018507:Gene Expression Regulation, Developmental; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000096:biosynthesis* / Q000235:genetics; D007596:Joints / Q000254:growth & development* / Q000378:metabolism / Q000503:physiopathology; D051379:Mice; D008822:Mice, Transgenic; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D015675:Osteocalcin / Q000378:metabolism; D010012:Osteogenesis / Q000235:genetics*
D015675:Osteocalcin; D007334:Insulin-Like Growth Factor I
Bone. 2008 Nov;43(5):869-79
18718566
Arthritis Rheum. 2006 Jun;54(6):1736-46
16729286
J Bone Miner Res. 2006 Apr;21(4):626-36
16598383
Arthritis Rheum. 2004 Oct;50(10):3354-64
15476255
Bone. 2013 Sep;56(1):184-90
23792936
Arthritis Rheum. 2000 Apr;43(4):844-51
10765929
Best Pract Res Clin Rheumatol. 2010 Jun;24(3):363-71
20534370
Ann Rheum Dis. 2007 Nov;66 Suppl 3:iii42-4
17934094
Ann Rheum Dis. 2014 Sep;73(9):1746-8
24845387
Nat Med. 2007 Jul;13(7):791-801
17618270
Endocr Rev. 2008 Aug;29(5):535-59
18436706
Biol Proced Online. 2012 Dec 19;14(1):10
23253472
Arthritis Rheum. 2012 Oct;64(10):3210-9
22736144
Scand J Rheumatol. 2012;41(6):421-5
22839688
Connect Tissue Res. 1989;20(1-4):277-82
2692956
Bone. 2006 Sep;39(3):494-504
16644298
Ann Rheum Dis. 2009 Jun;68(6):1044-50
18633128
Arthritis Rheum. 2009 Mar;60(3):717-27
19248087
Nat Med. 2007 Feb;13(2):156-63
17237793
Genes Dev. 1993 Dec;7(12B):2609-17
8276243
Autoimmunity. 2008 Apr;41(3):224-9
18365836
Clin Exp Rheumatol. 2009 Jul-Aug;27(4 Suppl 55):S10-4
19822039
J Bone Joint Surg Br. 2002 Mar;84(2):276-88
11922373