IGF-1 from bone marrow Adipoq-lineage cells stimulates endocortical bone formation in mature female mice

Insulin-like growth factor 1 (IGF-1) is an anabolic signal promoting growth, differentiation and function of both embryonic and postnatal tissues. Both endocrine and paracrine functions of IGF-1 have been documented to regulate bone growth and bone marrow hematopoiesis. Local production of IGF-1 from various cell types may contribute differently to the overall bioactivity of IGF-1 in bone, but relevant sources and mechanisms are yet to be fully elucidated. Here we report that the Adipoq+ stromal cells are a notable source of IGF-1 in the bone marrow of postnatal mice. Deletion of IGF-1 with Adipoq-Cre diminished endocortical bone formation and cortical bone mass in mature female mice. On the other hand, the trabecular bone parameters or hematopoietic properties were not affected in mutant mice of either sex. The study uncovers a local source of IGF-1 in the bone marrow microenvironment that contributes to bone anabolic regulation in a site-specific manner. Lay SummaryThe insulin-like growth factor 1 (IGF-1) is known to play important roles in promoting bone growth and in regulating blood stem or progenitor cells. The factor is available both through the blood circulation and from the local production by cells in the bone tissue, but the functional contribution of each source is not well understood. Here we discover the non-blood cells in the bone marrow (bone marrow stromal cells) as a notable source of IGF-1 which specifically stimulates bone formation in the bone shaft of the long bone.