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

Abstract

IntroductionInsulin 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.MethodsMice 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.Results90–100% 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.ConclusionOverexpression 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.

Inflammation Intensity–Dependent Expression of Osteoinductive Wnt Proteins Is Critical for Ectopic New Bone Formation in Ankylosing Spondylitis

“…First, low‐intensity constitutive inflammation might be the important driving factor for osteogenesis. Previously, data from animals with CIA were obtained over periods of no longer than 70 days after the last induction; thus, potential subsequent changes in the spine have not been reported . In this study, we extended the observational period to 30 weeks and found that spinal changes began at week 16 and that 40% of the experimental animals had spinal ankylosis at week 30 after induction (Figures A–C).…”