| Abstract: Objective Glucocorticoids (GCs) are widely used clinically in the treatment of inflammation-related diseases, but the long-term application of GCs leads to osteoporosis and osteoporosis-related fractures, known as glucocorticoid-induced osteoporosis (GIOP). Nr3c1 is the major glucocorticoid receptor. Its downstream signaling pathways are involved in regulating various intracellular physiological processes. The purpose of this study is to investigate the mechanism in glucocorticoid-induced osteoporosis (GIOP). Methods Zebrafish larvae were selected and randomly divided into WT group, 25 μmol/L PN treatment group, nr3c1-/-mutant group, and 25 μmol/L PN-treated nr3c1-/-mutant group, respectively. After 24 h fertilization, they were treated with PN (25 μmol/L). The sibling larvaeand in the control group received same amount of dimethyl sulfoxide (0.01%). The specimens were collected after 8 d fertilization (DPF) for overall bone staining. After 5 d and 8 d fertilization, the specimens were collected for quantitative reverse transcription (qRT-PCR) analysis. The effects of nr3c1 mutation on cartilage development and bone mineralization, and the expression of bone metabolism-related genes were evaluated. Results The expressions of extracellular matrix-, osteoblast-, and osteoclast-related genes were altered in the nr3c1-mutant. Further experiments revealed that GCs and Nr3c1 transcriptionally regulated matrix metallo-proteinase 9 (MMP9), alkaline phosphatase (ALP), and acid phosphatase 5a (ACP5a). Conclusion This study reveals that GCs/Nr3c1 affects the expression of genes involved in bone metabolism and provides a basis to determine the role of GIOP and Nr3c1 in bone metabolism and development. We also identified a new effector target for the clinical treatment of GIOP. |