biostudies-literatureBian FNational Institute of Arthritis and Musculoskeletal and Skin DiseasesHerman Ostrow School of Dentistry at the University of Southern CaliforniaOREFASBMR Fund for Research and Education Research and Collaborative GrantNIDCR NIH HHSFaculty Research Seed GrantStart-up FundNational Institute of Dental and Craniofacial ResearchNIAMS NIH HHS1644-1658https://www.ebi.ac.uk/biostudies/studies/S-EPMC11523133biostudies-literatureUnknown39(11)The cartilage growth plate is essential for maintaining skeletal growth; however, the mechanisms governing postnatal growth plate homeostasis are still poorly understood. Using approaches of molecular mouse genetics and spatial transcriptomics applied to formalin-fixed, paraffin-embedded tissues, we show that ADGRG6/GPR126, a cartilage-enriched adhesion G protein-coupled receptor (GPCR), is essential for maintaining slow-cycling resting zone cells, appropriate chondrocyte proliferation and differentiation, and growth plate homeostasis in mice. Constitutive ablation of Adgrg6 in osteochondral progenitor cells with Col2a1Cre leads to a shortened resting zone, formation of cell clusters within the proliferative zone, and an elongated hypertrophic growth plate, marked by limited expression of Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral ResearchThe G protein-coupled receptor ADGRG6 maintains mouse growth plate homeostasis through IHH signaling.PMC11523133R01AR072009R01 DE012711R00AR075899R00 AR077090R01DE012711R00AR077090R01 AR072009L40 AR079806Liu ZWu CLHe JFeng KHansen VFeng HCEbrahimi BChen YChai YBian FGray RSfalseThe G protein-coupled receptor ADGRG6 maintains mouse growth plate homeostasis through IHH signaling.The cartilage growth plate is essential for maintaining skeletal growth; however, the mechanisms governing postnatal growth plate homeostasis are still poorly understood. Using approaches of molecular mouse genetics and spatial transcriptomics applied to formalin-fixed, paraffin-embedded tissues, we show that ADGRG6/GPR126, a cartilage-enriched adhesion G protein-coupled receptor (GPCR), is essential for maintaining slow-cycling resting zone cells, appropriate chondrocyte proliferation and differentiation, and growth plate homeostasis in mice. Constitutive ablation of Adgrg6 in osteochondral progenitor cells with Col2a1Cre leads to a shortened resting zone, formation of cell clusters within the proliferative zone, and an elongated hypertrophic growth plate, marked by limited expression of 2024-01-01T00:00:00Z2024 Oct2025-04-04T03:01:06.61Z2025-04-04T03:01:06.61ZS-EPMC115231333923622010.1093/jbmr/zjae144