Regulation of body length and bone mass by Gpr126/Adgrg6
Open Access
- 20 March 2020
- journal article
- research article
- Published by American Association for the Advancement of Science (AAAS) in Science Advances
- Vol. 6 (12), eaaz0368
- https://doi.org/10.1126/sciadv.aaz0368
Abstract
Adhesion G protein–coupled receptor G6 (Adgrg6; also named GPR126) single-nucleotide polymorphisms are associated with human height in multiple populations. However, whether and how GPR126 regulates body height is unknown. In this study, we found that mouse body length was specifically decreased in Osx-Cre;Gpr126fl/fl mice. Deletion of Gpr126 in osteoblasts resulted in a remarkable delay in osteoblast differentiation and mineralization during embryonic bone formation. Postnatal bone formation, bone mass, and bone strength were also significantly affected in Gpr126 osteoblast deletion mice because of defects in osteoblast proliferation, differentiation, and ossification. Furthermore, type IV collagen functioned as an activating ligand of Gpr126 to regulate osteoblast differentiation and function by stimulating cAMP signaling. Moreover,the cAMP activator PTH(1–34), could partially restore the inhibition of osteoblast differentiation and the body length phenotype induced by Gpr126 deletion.Together, our results demonstrated that COLIV-Gpr126 regulated body length and bone mass through cAMP-CREB signaling pathway.Keywords
Funding Information
- National Natural Science Foundation of China (8171101485, 81722020)
- National Natural Science Foundation of China (91749204)
- National Natural Science Foundation of China (81830083)
- the national key Research and Development Program of China (2018YFC1105102)
- the national key Research and Development Program of China (2018YFC2001500)
- the national key Research and Development Program of China (2018YFA0507001)
- Shenzhen Municipal Government of China (KQTD20170810160226082)
- the Innovation Program of the Shanghai Municipal Education Commission (2017-01-07-00-05-E00011)
This publication has 40 references indexed in Scilit:
- The PERK-EIF2α-ATF4 signaling branch regulates osteoblast differentiation and proliferation by PTHAmerican Journal of Physiology-Endocrinology and Metabolism, 2019
- Endochondral ossification in hindlimbs during bufo gargarizans metamorphosis: A model of studying skeletal development in vertebratesDevelopmental Dynamics, 2018
- Parathyroid hormone regulates fates of murine osteoblast precursors in vivoJCI Insight, 2017
- Gpr126 Is Critical for Schwann Cell Function during Peripheral Nerve RegenerationJournal of Neuroscience, 2017
- IL-6 Enhances Osteocyte-Mediated Osteoclastogenesis by Promoting JAK2 and RANKL Activity In VitroCellular Physiology and Biochemistry, 2017
- Mutations of GPR126 Are Responsible for Severe Arthrogryposis Multiplex CongenitaAmerican Journal of Human Genetics, 2015
- GPR126 Protein Regulates Developmental and Pathological Angiogenesis through Modulation of VEGFR2 Receptor SignalingOnline Journal of Public Health Informatics, 2014
- Parathyroid Hormone Administration Improves Bone Marrow Microenvironment and Partially Rescues Haematopoietic Defects in Bmi1-Null MicePLOS ONE, 2014
- IL-6 negatively regulates osteoblast differentiation through the SHP2/MEK2 and SHP2/Akt2 pathways in vitroJournal of Bone and Mineral Metabolism, 2013
- Organ-specific function of adhesion G protein-coupled receptor GPR126 is domain-dependentProceedings of the National Academy of Sciences of the United States of America, 2013