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

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.