Table 1.
The functions and mechanisms of GPCR in mesenchymal stem cells (MSCs)
| GPCR Name | GRAFS Classification | Ligand | Coupled G Protein Subtype | Signaling Pathway | Functional/Phenotypic Changes and references |
|---|---|---|---|---|---|
| A1R (ADORA1) | Rhodopsin family - α subgroup (Amines) | Adenosine | Gαi | WNT signaling | Stimulates osteogenic differentiation in dental pulp stem cells 17. |
| A2AR (ADORA2A) | Rhodopsin family - α subgroup (Adenosine) | Adenosine | Gαs | cAMP/PKA | Increases proliferation and differentiation of bone marrow MSCs 18. |
| ADORA2B (A2BAR) | Rhodopsin family - α subgroup (Adenosine) | Adenosine | Gαs | Osteoblast differentiation gene regulation | Deletion lowers bone mineral density and reduces mineralization in BMSCs 19. |
| ADRB2 (β-AR) | Rhodopsin family - α subgroup (Adrenergic) | Norepinephrine, Isoproterenol, Epinephrine | Gαs | cAMP/PKA | Agonists inhibit mineralization and osteogenesis; antagonists promote mineralization 22, 23. |
| CaSR | Glutamate family | Extracellular Ca²⁺ | Gαq/Gαi | Calcium sensing → PTHrP/PTH1R inhibition | Maintains osteogenic potential; knockdown reduces bone formation capacity 15. |
| EP1 | Rhodopsin family | PGE2 | Gαq/11 | ↑ PLCβ → IP₃/DAG → Ca²⁺ release, PKC activation | Inhibits osteoblast migration, exacerbates osteoarthritis 20, 21. |
| EP2/EP4 (PTGER) | Rhodopsin family | PGE2 | Gαs | FAK/ERK1/2 → PGE2 release | Enhances MSC migration; boosts immunosuppressive effects on RA T cells 27, 28. |
| GPR161 | Other 7TM receptors | / | Gαs | Mechanical force → cAMP signaling | Knockdown impairs mechanotransduction and reduces osteogenic marker expression 29. |
| GPRC6A | Glutamate family | cation, amino acid, and testosterone | Gαq (putative) | Extracellular calcium → ERK activation | Promotes osteogenic marker expression and mineralization; knockout reduces bone mineral density 16. |
| LGR5 (GPR49) | Adhesion family | R-spondin | Gαs (putative) | Wnt/β-catenin, ERK, mitochondrial dynamics | Promotes osteogenic differentiation of MSCs; overexpression accelerates fracture healing 14. |
| LPAR1 (EDG2/GPCR26) | Rhodopsin family - δ subgroup (Lipids) | Lysophosphatidic acid, LPA | Gα12/Gα13 (major), Gαq/Gαi (minor) | Caspase-3 inhibition → anti-apoptosis | Protects MSCs from apoptosis; promotes proliferation 26. |
| PTH1R | Secretin family | PTH/ PTHrP | Gαs | cAMP/PKA → Runx2/osteocalcin | Enhances osteogenic differentiation and bone formation; inhibits osteoclastogenesis 6, 15. |