Objective <p>Osteoporosis (OP) is a systemic bone disease without effective treatment at present. The aim of this study is to explore the role of the circular RNA GCLC (circGCLC) in the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs).</p> Methods <p>The expression of circGCLC, miR-516b-5p, and the G protein alpha subunit (GNAS) was determined during osteogenic differentiation of BMSCs. Plasmid or oligonucleotide transfection was used to modify the expression levels of circGCLC, miR-516b-5p, and GNAS for assessing their effects on osteogenic differentiation ability, osteogenesis-related proteins, and MAPK signalling pathway-related proteins in BMSCs. The interactions among circGCLC, miR-516b-5p, and GNAS were also investigated.</p> Results <p>During osteogenic differentiation of BMSCs, circGCLC and GNAS levels increased, whereas miR-516b-5p expression decreased. The knockdown of circGCLC inhibited osteogenic differentiation and MAPK signalling pathway activation in BMSCs. The increase in osteogenic differentiation that was induced by circGCLC upregulation was reversed by overexpressing miR-516b-5p. The inhibitory effects of circGCLC silencing on BMSC osteogenic differentiation were counteracted by GNAS upregulation. CircGCLC competitively bound to miR-516b-5p, mediating GNAS expression.</p> Conclusion <p>CircGCLC activates the MAPK signalling pathway by sponging miR-516b-5p, which mediates GNAS expression, thereby promoting the osteogenic differentiation of BMSCs.</p>