GPR133 (ADGRD1) – A POTENTIAL TARGET IN THE TREATMENT OF OSTEOPOROSIS
DOI:
https://doi.org/10.11603/1811-2471.2026.v.i1.15703Keywords:
GPR133, ADGRD1, adhesion GPCR, osteogenesis, osteoblasts, osteoporosis, mechanosensitivity, receptor agonist AP503Abstract
SUMMARY. The aim – to systematise data from reviews and studies devoted to the role of the adhesive G protein receptor GPR133 in the regulation of osteogenesis and its potential as a target for the treatment of osteoporosis.
Material and Methods. A literature search was conducted in the PubMed, Scopus, and Web of Science databases for the period 2014–2025 using combinations of the keywords: “GPR133”, “ADGRD1”, “adhesion GPCR”, “G-protein coupled receptor”, “osteogenesis”, “osteoporosis”. The analysis included 20 sources – systematic reviews, experimental studies, and patent materials that met the study criteria and contained data on the role of GPR133 or related adhesion GPCRs in the regulation of osteogenesis.
Results. Adhesion G-protein-coupled receptors GPR133/ADGRD1 due to the presence of mechanosensitive metabolotropic properties are considered as regulators of bone remodeling. The GPR133/ADGRD1 protein gene has been identified in the tibia, femur, skull, and costal cartilage. The mRNA of this gene has been identified in bone marrow mesenchymal stem cells, primary osteoblasts, osteoclasts, and bone marrow macrophages. The activity of GPR133 depends on both the presence of a ligand and mechanical stress or strain. Receptor activation is realized directly through changes in the tension of the membrane lipid bilayer or through the transmission of mechanical force due to the attachment of the receptor to the cytoskeleton or extracellular matrix. GPR133 deficiency in mice leads to a decrease in trabecular and cortical bone mass, impaired osteoblastogenesis, and compensatory activation of osteoclasts, confirming its key role in maintaining bone homeostasis. Small-molecule GPR133 agonists, such as AP503 and GL64, stimulate osteoblastogenesis, increase bone mass and bone strength, and show synergy with exercise.
Conclusions. GPR133/ADGRD1 is a proven molecular target for osteoporosis therapy: its deficiency reduces bone mass and strength due to osteoblast dysfunction. The use of selective GPR133 agonists opens up new pathogenetical directions for the treatment of osteoporosis, avoiding the potential risks inherent in traditional therapeutic regimens.
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