BoneKEy Reports | BoneKEy Watch
Insulin-like growth factor 1 is a key regulator of bone mass
DOI:10.1038/bonekey.2012.173
Xian et al. generated knockout mice that were unable to express the receptor for insulin-like growth factor 1 (IGF-1) in their pre-osteoblastic cells to find out more about the impact of IGF-1 on bone remodeling. Not surprisingly, as IGF-1 maintains bone mass in adult humans, Igf1r knockout mice had reduced bone mass and lower rates of mineral disposition than controls. This was due to a lower number of mature osteoblasts.
When bone marrow cells were isolated and sorted by flow cytometry, the authors identified cells from the hematopoietic lineage (Sca-1+, CD29+, CD45− and CD11b−). On treatment with rapamycin, an mTOR inhibitor, these cells could not mediate the mineralization normally inducible by IGF-1 but survived and grew normally.
Further experiments revealed that IGF-1 activates mTOR via the IRS1-P13K-Akt pathway and so is able to control the differentiation of osteoblasts, and therefore to regulate bone formation. The authors also demonstrated that the level of IGF-1 in the bone matrix is directly correlated with bone mass.
Editor's comment: This study clearly demonstrates that matrix IGF-1 released during bone remodeling enhances differentiation of pre-osteoblastic cells by stimulating the mTOR pathway. Considering the reported interaction of osteoclast-derived Sema4D with IGF-1 signaling via IRS-1 phosphorylation, this finding suggests that matrix IGF-1 is a key player in maintaining the coupling of bone remodeling.
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