BoneKEy Reports | BoneKEy Watch
Osteoblasts: skeletal controllers of energy metabolism
DOI:10.1038/bonekey.2012.11
Bone is emerging as an important endocrine tissue; osteoblasts produce osteocalcin, a hormone that increases the body's sensitivity to insulin and the production of insulin, promotes beta cell expansion and boosts energy expenditure. Yoshikawa et al. tested the hypothesis that fewer osteoblasts might mean reduced energy metabolism by breeding two strains of transgenic mice, one expressing a tamoxifen-regulated CRe controlled by the osteocalcin promoter, the other with an inactive form of the diphtheria A toxin chain. Treatment of double mutant progeny with tamoxifen reduced osteoblasts by 55%, an efficient partial ablation.
Osteoblast ablation had a significant effect on mouse metabolism; insulin secretion was reduced and the animals showed clear hyperglycaemia, glucose intolerance and decreased insulin sensitivity. These effects have been noted in osteocalcin-deficient mice but osteoblast-ablated mice also showed a decrease in gonadal fat, increased energy expenditure and their expression of resistin, a putative mediator of insulin resistance, rose. Osteoblast ablation also reduced testosterone levels in male mice.
When the mice were injected with osteocalcin, glucose intolerance was completely reversed and insulin and blood sugar levels normalised. Osteocalcin also restored testosterone levels, confirming recent observations that the osteocalcin produced by the skeleton has an impact on male fertility.
Editor's comment: Gonadal fat and energy expenditure were not affected, suggesting that osteoblasts play a key role in the metabolic control of fat and that they secrete other, as yet unidentified, energy metabolism-regulating hormones.
This work is licensed under a
Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 United States License.