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Liver-derived IGF-I is not required for protection against osteoarthritis in male mice.

Journal article
Authors Anna E Törnqvist
Antonia Sophocleous
Stuart H Ralston
Claes Ohlsson
Johan Svensson
Published in American journal of physiology. Endocrinology and metabolism
Volume 317
Issue 6
Pages E1150-E1157
ISSN 1522-1555
Publication year 2019
Published at Centre for Bone and Arthritis Research
Institute of Medicine, Department of Internal Medicine and Clinical Nutrition
Pages E1150-E1157
Language en
Links dx.doi.org/10.1152/ajpendo.00330.20...
www.ncbi.nlm.nih.gov/entrez/query.f...
Subject categories Endocrinology

Abstract

Insulin-like growth factor-I (IGF-I) is anabolic for cartilage and important for cartilage integrity, which might suggest a connection between IGF-I and osteoarthritis (OA) development. However, the results of studies performed so far are conflicting, and we aimed to clarify the role of endocrine IGF-I in rodent OA. Male mice with inducible inactivation of circulating, liver-derived IGF-I (LI-IGF-I-/- mice, serum IGF-I reduced by ~80%) were used. Experimental OA was induced in young adult LI-IGF-I-/- and control mice by destabilization of the medial meniscus (DMM); age-related OA was also evaluated in 1-yr-old mice. DMM-operated LI-IGF-I-/- mice had thinner lateral subchondral bone plate in tibia compared with control mice, whereas osteophyte volume and articular cartilage damage were unaffected at the medial side of the DMM knee. However, the control mice but not the LI-IGF-I-/- mice also developed mild OA on the lateral side of the DMM knee compared with the unoperated knee. One-year-old LI-IGF-I-/- mice had lower mid-diaphyseal cortical bone area than the 1-yr-old control mice, whereas analyses of joint tissues displayed smaller osteophyte volume and thicker calcified cartilage than the control mice. There was no difference in OA severity in the articular cartilage between old LI-IGF-I-/- and control mice. Our study is the first to investigate whether there is an association between circulating IGF-I and OA in mice. We conclude that, although there is an ~80% reduction of circulating IGF-I and a decrease in cortical bone in male LI-IGF-I-/- mice, cartilage damage is clearly not intensified and may instead be slightly reduced.

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