The G-protein-coupled receptor GPR103 regulates bone formation.
GPR103 is a G-protein-coupled receptor with reported expression in brain, heart, kidney, adrenal gland, retina, and testis. It encodes a 455-amino-acid protein homologous to neuropeptide FF2, neuropeptide Y2, and galanin GalR1 receptors. Its natural ligand was recently identified as 26RFa, a novel human RF-amide-related peptide with orexigenic activity. To identify the function of GPR103, we generated GPR103-deficient mice. Homozygous mutant mice were viable and fertile. Their body weight was undistinguishable from that of their wild-type littermates. Histological analysis revealed that GPR103-/- mice exhibited a thinned osteochondral growth plate, a thickening of trabecular branches, and a reduction in osteoclast number, suggestive of an early arrest of osteochondral bone formation. Microcomputed tomography confirmed the reduction in trabecular bone and connective tissue densities in GPR103 knockout animals. Whole-body radiography followed by morphometric analysis revealed a kyphosis in mutant animals. Reverse transcription-PCR analysis showed that GPR103 was expressed in human skull, mouse spine, and several osteoblast cell lines. Dexamethasone, a known inhibitor of osteoblast growth and inducer of osteoblast differentiation, inhibited GPR103 expression in human osteoblast primary cultures. Altogether, these results suggest that osteopenia in GPR103-/- mice may be mediated directly by the loss of GPR103 expression in bone.
Baribault
Helene
H
Department of Biology Research, Amgen, Mail Stop ASF1-1, 1120 Veterans Blvd., South San Francisco, California 94080, USA. helene@amgen.com
Danao
Jean
J
Gupte
Jamila
J
Yang
Li
L
Sun
Banghua
B
Richards
William
W
Tian
Hui
H
D000818:Animals; D015519:Bone Density; D001842:Bone and Bones / Q000378:metabolism; D001921:Brain / Q000378:metabolism; D002454:Cell Differentiation; D002460:Cell Line; D005260:Female; D006132:Growth Plate / Q000502:physiology; D006801:Humans; D007668:Kidney / Q000378:metabolism; D007738:Kyphosis / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009928:Organ Specificity; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism; D010010:Osteoclasts / Q000166:cytology / Q000378:metabolism; D010012:Osteogenesis / Q000502:physiology*; D010052:Ovariectomy; D043562:Receptors, G-Protein-Coupled / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D012886:Skull / Q000378:metabolism; D013131:Spine / Q000000981:diagnostic imaging / Q000378:metabolism; D014057:Tomography, X-Ray Computed
C476583:Qrfpr protein, mouse; D043562:Receptors, G-Protein-Coupled