The P2Y13 receptor regulates phosphate metabolism and FGF‐23 secretion with effects on skeletal development. Issue 5 (31st January 2014)

• Record Type: Journal Article
• Authors: Wang, Ning; Robaye, Bernard; Gossiel, Fatima; Boeynaems, Jean‐Marie; Gartland, Alison
• Is Part Of: FASEB journal. Volume 28:Issue 5(2014)
• Page Start: 2249
• Page End: 2259
• Publication Date: 2014-01-31
• Subjects: knockout -- bone phenotype -- purinergic -- ADP; Biology -- Periodicals; Biology, Experimental -- Periodicals; 570
• DOI: 10.1096/fj.13-243626
• Languages: English
• ISSNs: 0892-6638

Abstract

ABSTRACT: Purinergic signaling mediates many cellular processes, including embryonic development and regulation of endocrine signaling. The ADP P2Y13 receptor is known to regulate bone and stem cells activities, although relatively little is known about its role in bone development. In this study we demonstrate, using contemporary techniques, that deletion of the P2Y13 receptor results in an age‐dependent skeletal phenotype that is governed by changes in phosphate metabolism and hormone levels. Neonatal and postnatal (2 wk) P2Y13 receptor‐knockout (KO) mice were indistinguishable from their wild‐type (WT) littermate controls. A clear bone phenotype was observed in young (4‐wk‐old) KO mice compared WT controls, with 14% more trabecular bone, 35% more osteoblasts, 73% fewer osteoclasts, and a 17% thicker growth plate. Mature (>10 wk of age) KO mice showed the opposite bone phenotype, with 14% less trabecular bone, 22% fewer osteoblasts, and 10% thinner growth plate. This age‐dependent phenotype correlated with serum fibroblast growth factor‐23 (FGF‐23) and phosphorus levels that were 65 and 16% higher, respectively, in young KO mice but remained unchanged in mature mice. These findings provide novel insights for the role of the P2Y13 receptor in skeletal development via coordination with hormonal regulators of phosphate homeostasis.—Wang, N., Robaye, B., Gossiel, F., Boeynaems, J.‐M., Gartland, A. The P2Y13 receptor regulates phosphate metabolism and FGF‐23 secretion with effects on skeletal development. FASEB J . 28, 2249–2259 (2014). www.fasebj.org