ADGRG1/GPR56 in cartilage bioengineering: A potential marker for superior chondrogenesis

To repair excised portions of the nose in non-melanoma skin cancer, surgeons have begun to use tissue-engineered nasal cartilage autografts. While promising, this approach has been hindered by significant inter-donor variability of cartilage quality within the autografts. For this approach to become clinically viable, there is a need to pre-select nasal chondrocytes with the capacity to create high-quality cartilage for autograft engineering. Recently, using RNA sequencing of clonal nasal chondrocyte populations, we have discovered G protein-coupled receptor 56 (aka ADGRG1 ) expression to be positively correlated with glycosaminoglycan per DNA (cellular content) and SOX9 expression, both are metrics of chondrogenic capacity. This correlation suggests G protein-coupled receptor 56 holds promise to be a marker of nasal chondrocytes with the capacity to produce high quality cartilage. G protein-coupled receptor 56 has been extensively studied in fields such as neural development, hematopoiesis, and cancer but is unreported within the cartilage biology field. This narrative review examines the molecular, cellular and physiological literature of G protein-coupled receptor 56, including some of its known ligands: collagen III, transglutaminase 2, testosterone, and signaling pathways: Ras homolog gene family, member A/Rho-associated protein kinase, phosphoinositide 3-kinase/AKT/mechanistic target of rapamycin, Nuclear Factor of Activated T-cells, cyclic adenosine monophosphate/protein kinase A. We then integrate the literature of these ligands and signaling pathways from the cartilage biology field to hypothesize the specific cellular and physiological role of G protein-coupled receptor 56 within cartilage. Ultimately, this review highlights the promise of G protein-coupled receptor 56 as a cell marker for high-quality cartilage production, we emphasize the need for further empirical investigation of G protein-coupled receptor 56 in the cartilage.