ArticleJournal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research2024
The G protein-coupled receptor ADGRG6 maintains mouse growth plate homeostasis through IHH signaling.
Article in Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it.
- "Quiescence" in the resting zone of the growth plate: a systematic review.Stem cells (Dayton, Ohio) · 2026Pooled it
- The regulatory significance of chondrocyte hypertrophy in maintaining chondrocyte homeostasis, regeneration and repair.Future science OA · 2026Review
- Integrated transcriptomic and functional analysis reveals tissue-specific molecular pathology in adolescent idiopathic scoliosis.HGG advances · 2026Article
- Traditional Chinese Medicine for the prevention and treatment of adolescent idiopathic scoliosis: scientific understanding and a multimodal therapeutic approach.Journal of traditional Chinese medicine = Chung i tsa chih ying wen pan · 2026Review
- Adhesion G protein-coupled receptors.Pharmacological reviews · 2026Review
- Genetic interaction betweenResearch square · 2026Article
- Genetic interaction betweenbioRxiv : the preprint server for biology · 2026Article
- Review
- Distinct Biological and Biomechanical Features in TMJ and Knee Cartilages.bioRxiv : the preprint server for biology · 2026Article
- Advances in Spatial Transcriptomics in Bone.Current osteoporosis reports · 2026Review
- G protein-coupled receptor signaling in osteogenic bone mesenchymal stem/stromal cells.Frontiers in cell and developmental biology · 2026Review
- A self-limiting mechanotransduction feedback loop ensures robust organ formation.bioRxiv : the preprint server for biology · 2025Article
- In situ implantation of type II collagen-based double-layer scaffolds for Articular Osteochondral Regeneration comprising hyaline cartilage and vascularized subchondral bones.Bioactive materials · 2025Article
- Spatial transcriptomic applications in orthopedics.Connective tissue research · 2025Review
- Advances in spatial transcriptomics and its application in the musculoskeletal system.Bone research · 2025Review
- Recent advances in omics and the integration of multi-omics in osteoarthritis research.Arthritis research & therapy · 2025Review
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Authors and funding
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Abstract
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 parathyroid hormone-related protein (PTHrP) but increased Indian Hedgehog (IHH) signaling throughout the growth plate. Attenuation of smoothened-dependent hedgehog signaling restored the Adgrg6 deficiency-induced expansion of hypertrophic chondrocytes, confirming that IHH signaling can promote chondrocyte hypertrophy in a PTHrP-independent manner. In contrast, postnatal ablation of Adgrg6 in mature chondrocytes with AcanCreERT2, induced after the formation of the resting zone, does not affect PTHrP expression but causes an overall reduction of growth plate thickness marked by increased cell death specifically in the resting zone cells and a general reduction of chondrocyte proliferation and differentiation. Spatial transcriptomics reveals that ADGRG6 is essential for maintaining chondrocyte homeostasis by regulating osteogenic and catabolic genes in all the zones of the postnatal growth plates, potentially through positive regulation of SOX9 expression. Our findings elucidate the essential role of a cartilage-enriched adhesion GPCR in regulating cell proliferation and hypertrophic differentiation by regulation of PTHrP/IHH signaling, maintenance of slow-cycle resting zone chondrocytes, and safeguarding chondrocyte homeostasis in postnatal mouse growth plates.
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