Online Methods

Animals. We obtained Rag mice from the Mouse Models of Human Cancers Consortium Repository, US National Cancer Institute. Igf1r and Osx1-GFP:Cre (The Jackson Laboratory) mouse lines have been described previously. To generate Osx-Cre; Igf1r (Igf1r) mice, we crossed hemizygous Osx-Cre transgenic mice with Igf1r mice to generate heterozygous Igf1r-flox offspring with and without a Cre allele. We then intercrossed these offspring to generate the following offspring: Osx-Cre; Igf1r (conditional knockout mice referred as Igf1r), Osx-Cre (referred as Igf1r), Osx-Cre; Igf1r (heterozygous conditional Knockout mice, referred as Igf1r), and mice without Osx-Cre. The liver-specific Igf-1 deletion (LID) mice were created by crossing the mice expressing Cre-recombinase under the albumin enhancer/promoter (The Jackson Laboratory) with the mice floxed exon 4 of the Igf-1 gene. We performed genotyping using the genomic DNA isolated from tail biopsies. We purchased different aged male Sprague Dawley rats from the Harlan Laboratories, and used 20 months old rats in the local injection experiment. The average body weight of the old rats was 675 ± 25 g. All animals were maintained in the Animal Facility of the Johns Hopkins University School of Medicine. The experimental protocol was reviewed and approved by the Institutional Animal Care and Use Committee of the Johns Hopkins University, Baltimore, MD, USA.