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Calcitonin acts on osteoclasts to regulate bone formation
DOI:10.1038/bonekey.2015.25
Keller et al. generated mice with a deletion of the calcitonin binding site in the calcitonin receptor (CTR) to find out why the absence of calcitonin (CT) expression in vivo leads to enhanced bone formation despite this hormone acting as a pharmacological inhibitor of bone resorption.
They demonstrated that CTR increases bone formation by reducing the expression of sphingosine1-phosphate (S1P), a signalling lipid, in osteoclasts. Five S1P receptors are known; further experiments showed that S1P3 was the most likely to be involved in the control of bone formation. Mice lacking CTR and therefore with raised S1P levels were bred to generate a strain with an S1P3 deletion; the skeletal phenotype of these mice was normal.
Immunochemistry studies also revealed that S1P3 could be detected in the spinal bone of wild-type mice and in iliac crest tissue from patients with Paget’s disease of the bone.
Editor’s comment: S1P has recently been shown to be an important clastokine. Its activity explains the enhanced coupling between osteoclasts and bone formation that is observed with cathepsin K deficiency. This study now extends our knowledge of the mechanisms by which S1P levels are controlled, revealing more about the role of calcitonin in bone formation. It also suggests that S1P3 warrants further investigation as a therapeutic target in disorders that result in bone loss.
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