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

PLoS One. 2016 Oct 3;11(10):e0163632. doi: 10.1371/journal.pone.0163632. eCollection 2016.

Abstract

Introduction: 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.

Conclusion: 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.

MeSH terms

  • Animals
  • Arthritis, Experimental / genetics*
  • Arthritis, Experimental / physiopathology
  • Cartilage / growth & development
  • Cartilage / metabolism
  • Cell Differentiation / genetics
  • Cell Line
  • Chondrocytes / metabolism
  • Chondrocytes / pathology
  • Disease Models, Animal
  • Gene Expression Regulation, Developmental
  • Humans
  • Insulin-Like Growth Factor I / biosynthesis*
  • Insulin-Like Growth Factor I / genetics
  • Joints / growth & development*
  • Joints / metabolism
  • Joints / physiopathology
  • Mice
  • Mice, Transgenic
  • Osteoblasts / metabolism
  • Osteoblasts / pathology
  • Osteocalcin / metabolism
  • Osteogenesis / genetics*

Substances

  • Osteocalcin
  • Insulin-Like Growth Factor I

Grant support

DB is supported by a VICI grant from the Netherlands Scientific Organization (NWO) and a Consolidator grant from the European Research Council (ERC). MT is supported by a grant from the Dutch Arthritis Association.