Insulin-Like Growth Factor I Does Not Drive New Bone Formation in Experimental Arthritis

• Published in: PloS one Vol. 11; no. 10; p. e0163632
• Main Authors: van Tok, Melissa N, Yeremenko, Nataliya G, Teitsma, Christine A, Kream, Barbara E, Knaup, Véronique L, Lories, Rik J, Baeten, Dominique L, van Duivenvoorde, Leonie M
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 03.10.2016; Public Library of Science (PLoS)
• Subjects: Aging; Analysis; Animal models; Animals; Ankle; Arthritis; Arthritis, Experimental - genetics; Arthritis, Experimental - physiopathology; Biocompatibility; Biology and Life Sciences; Biomedical materials; Bone growth; Bone healing; Cartilage; Cartilage - growth & development; Cartilage - metabolism; Cell Differentiation - genetics; Cell Line; Chondrocytes; Chondrocytes - metabolism; Chondrocytes - pathology; Collagen; Disease; Disease Models, Animal; Gene Expression Regulation, Developmental; Genetic engineering; Genotype & phenotype; Humans; Immunology; Inflammation; Inflammatory diseases; Insulin; Insulin-like growth factor I; Insulin-Like Growth Factor I - biosynthesis; Insulin-Like Growth Factor I - genetics; Insulin-like growth factors; Joint diseases; Joints - growth & development; Joints - metabolism; Joints - physiopathology; Lories; Medicine and Health Sciences; Melanoma; Mice; Mice, Transgenic; Osteoblasts; Osteoblasts - metabolism; Osteoblasts - pathology; Osteocalcin; Osteocalcin - metabolism; Osteogenesis; Osteogenesis - genetics; Pathology; Repair; Research and Analysis Methods; Rheumatic diseases; Rheumatoid arthritis; Rheumatoid factor; Rheumatology; Rodents; Teaching hospitals; Transgenic animals; Tumor necrosis factor-TNF; Belgium; Netherlands
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0163632

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. 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. 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. 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.