Calcitonin (CT) is known to inhibit bone resorption. Scientists at Helmholtz Zentrum München, in cooperation with colleagues from the University Hospital Hamburg-Eppendorf, have now discovered that inactivation of the calcitonin receptor can lead to increased bone formation. In terms of translational research this could represent a new approach for the treatment of osteoporosis.
The scientists showed for the first time that the reduction of CT in the murine model led to increased bone mineral density. Osteoclast-specific inhibition of the CT receptor was sufficient to initiate this phenotypic expression. Inactivation of the CT receptor directly caused a clear increase in bone mass. At the same time an increase in sphingosine-1-phosphate (S1P) was observed. When the S1P receptor S1P3 was deleted, the bone mineral density did not change.
“These studies redefine the role of CT in the biology of bone synthesis,” said Prof. Dr. Martin Hrabě de Angelis, director of the Institute of Experimental Genetics at Helmholtz Zentrum München (HMGU), who conducted research on this question together with the Hamburg scientists and his Munich colleagues from the Institute of Pathology (HMGU) and researchers from the Department of Molecular Animal Breeding and Biotechnology of Ludwig-Maximilians-Universität München. “We see here that S1P acts as an osteo-anabolic molecule in vivo,” said Martin Hrabě de Angelis. “This crosstalk between osteoclasts and osteoblasts might offer opportunities for a pharmacologically intervention, leading to a basis for the treatment of osteoporosis.”
Calcitonin controls bone formation by inhibiting the release of sphingosine 1-phosphate from osteoclasts. Keller et al., NATURE COMMUNICATIONS | 5:5215 | DOI: 10.1038/ncomms6215