Bone is a dynamic structure that undergoes constant bone remodelling. Bone remodelling is regulated by a balance between osteoblastic formation and osteoclastic resorption. Zinc, an essential trace element, is important regulator of bone homeostasis. Recently, a receptor specifically activated by zinc was identified. This receptor named GPR39 belongs to the G Protein Coupled Receptor (GPCR) superfamily. However, a role of GPR39 in regulation of bone metabolism was not explored. In order to elucidate a role for GPR39 in bone metabolism we investigated the bone phenotype of GPR39 deficient mice. These mice had normal body length and weight. However, micro CT analysis of trabecular bone in the femurs of six month old mice revealed a significant 32% increase in trabecular bone fraction compared to wild type littermates. Increased trabecular bone in these mice was a result of higher trabecular number and trabecular thickness. In order to test whether increased bone mass was a result of attenuated resorption by osteoclasts we analysed serum levels of CTX-1 peptide, a marker for bone resorption. CTX-1 levels in GPR39 deficient mice were lower but did not reach statistical significance. On the other hand, serum levels of PINP-1, a marker for bone formation, showed a significant 26% increase in GPR39 deficient mice indicating an increase of bone formation. We compared the mineral secretion of osteoblasts isolated from bone marrow of GPR39 deficient and wild-type mice. The intensity of mineral staining was higher in cultures of GPR39 deficient osteoblasts suggesting an increased function of GPR39 deficient osteoblasts. Our data reveal a novel role for the zinc receptor GPR39 in regulation of bone homeostasis and suggest that its absence leads to excessive bone formation by osteoblasts.
Disclosure: The authors declared no competing interests.