Journal Article

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

Yeremenko, Nataliya G., van Duivenvoorde, Leonie M., Lories, Rik J., Teitsma, Christine A., Baeten, Dominique L., van Tok, Melissa N., Kream, Barbara E., Knaup, Véronique L.

2016

Overview

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.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: 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