University of Oulu

Johan Svensson, Klara Sjögren, Lina Lawenius, Antti Koskela, Juha Tuukkanen, Karin H Nilsson, Sofia Movérare-Skrtic, Claes Ohlsson, Bone-Derived IGF-I Regulates Radial Bone Growth in Adult Male Mice, Endocrinology, Volume 164, Issue 8, August 2023, bqad104,

Bone-derived IGF-I regulates radial bone growth in adult male mice

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Author: Svensson, Johan1; Sjögren, Klara1; Lawenius, Lina1;
Organizations: 1Centre for Bone and Arthritis Research, Department of Internal Medicine and Clinical Nutrition, Institute of Medicine, Sahlgrenska Academy, University of Gothenburg, 413 45 Gothenburg, Sweden
2Department of Anatomy and Cell Biology, Institute of Cancer Research and Translational Medicine, Medical Research Center, University of Oulu, 90014 Oulu, Finland
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Version: published version
Access: open
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Language: English
Published: Endocrine Society, 2023
Publish Date: 2023-11-02


Insulin-like growth factor-I (IGF-I) levels, which are reduced by age, and cortical bone dimensions are major determinants of fracture risk in elderly subjects. Inactivation of liver-derived circulating IGF-I results in reduced periosteal bone expansion in young and older mice. In mice with lifelong depletion of IGF-I in osteoblast lineage cells, the long bones display reduced cortical bone width. However, it has not previously been investigated whether inducible inactivation of IGF-I locally in bone in adult/old mice affects the bone phenotype. Adult tamoxifen-inducible inactivation of IGF-I using a CAGG-CreER mouse model (inducible IGF-IKO mice) substantially reduced IGF-I expression in bone (−55%) but not in liver. Serum IGF-I and body weight were unchanged. We used this inducible mouse model to assess the effect of local IGF-I on the skeleton in adult male mice, avoiding confounding developmental effects. After tamoxifen-induced inactivation of the IGF-I gene at 9 months of age, the skeletal phenotype was determined at 14 months of age. Computed tomography analyses of tibia revealed that the mid-diaphyseal cortical periosteal and endosteal circumferences and calculated bone strength parameters were decreased in inducible IGF-IKO mice compared with controls. Furthermore, 3-point bending showed reduced tibia cortical bone stiffness in inducible IGF-IKO mice. In contrast, the tibia and vertebral trabecular bone volume fraction was unchanged. In conclusion, inactivation of IGF-I in cortical bone with unchanged liver-derived IGF-I in older male mice resulted in reduced radial growth of cortical bone. This suggests that not only circulating IGF-I but also locally derived IGF-I regulates the cortical bone phenotype in older mice.

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Series: Endocrinology
ISSN: 0013-7227
ISSN-E: 1945-7170
ISSN-L: 0013-7227
Volume: 164
Issue: 8
Article number: bqad104
DOI: 10.1210/endocr/bqad104
Type of Publication: A1 Journal article – refereed
Field of Science: 3121 General medicine, internal medicine and other clinical medicine
Funding: This work was supported by the Swedish state under the agreement between the Swedish government and the county councils, the ALF-agreement (ALFGBG-965744).
Copyright information: © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (, which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited.