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Updated: Sep 10, 2025
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A Kinetic Fluorescence-based Ca2+ Mobilization Assay to Identify G Protein-coupled Receptor Agonists, Antagonists, and Allosteric Modulators
Published on: February 20, 2018
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The function of GPCRs in different bone cells.
Yan Zhang1,2, Nai-Ning Wang1,3, Zi-Han Qiu1
1Key Laboratory of Biomedical Information Engineering of Ministry of Education, Key Laboratory of Biology Multiomics and Diseases in Shaanxi Province Higher Education Institutions, and Biomedical Informatics & Genomics Center, School of Life Science and Technology, Xi'an Jiaotong University, Xi'an, Shaanxi, 710049, China.
International Journal of Biological Sciences
|August 27, 2025
Summary
G protein-coupled receptors (GPCRs) are key targets for bone disorders. This review details GPCRs in bone cells, offering insights into new therapies for skeletal diseases like osteoporosis and arthritis.
Area of Science:
- Skeletal Biology and Pharmacology
- Cellular and Molecular Medicine
Background:
- G protein-coupled receptors (GPCRs) play crucial roles in regulating bone cell function and skeletal homeostasis.
- Dysregulation of GPCR signaling is implicated in various bone disorders, highlighting their therapeutic potential.
Purpose of the Study:
- To systematically review and catalog GPCR expression and function across diverse bone cell types.
- To elucidate the molecular mechanisms by which GPCRs coordinate cellular plasticity for skeletal health.
- To provide a framework for advancing GPCR-targeted therapies for bone-related diseases.
Main Methods:
- Systematic review of GPCR expression and functional roles in mesenchymal stem cells, osteoblasts, osteocytes, macrophages, osteoclasts, and chondrocytes.
- Integration of canonical signaling pathways including cAMP/PKA, PLC-β/IP3, and NF-κB.
- Analysis of GPCR involvement in skeletal homeostasis and disease pathogenesis.
Main Results:
- Cataloged specific numbers of GPCRs and their functions in different bone cell lineages (e.g., 12 in MSCs, 21 in osteoblasts/osteocytes, 23 in macrophages/osteoclasts, 31 in chondrocytes).
- Demonstrated how GPCRs dynamically regulate cellular plasticity through integrated signaling axes.
- Identified GPCRs as critical regulators of matrix mineralization, mechanotransduction, inflammatory bone resorption, and endochondral ossification.
Conclusions:
- GPCRs are central regulators of skeletal homeostasis, with distinct expression patterns and functions across bone cell types.
- Understanding GPCR signaling provides a foundation for developing novel therapeutic strategies for bone disorders.
- Precision strategies like biased agonism and allosteric modulation offer promising avenues for clinical translation in osteoporosis, arthritis, and regenerative medicine.
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