CREG1 promotes bone formation via targeting RAB7 to activate autophagy in osteoporosis

Osteoporosis is characterized by reduced bone mass and impaired skeletal microarchitecture, with impaired osteogenic differentiation capacity of bone marrow mesenchymal stem cells (BMSCs) serving as a key contributing factor in its development. Cellular repressor of E1A-stimulated genes 1 (CREG1), a lysosomal glycoprotein, has been implicated in the regulation of autophagy and osteogenic differentiation. However, the molecular mechanisms underlying CREG1-mediated bone homeostasis remain unclear. In this study, we identified RAB7, a small GTPase involved in endosomal trafficking and autophagy, as a downstream effector of CREG1. We found that RAB7 expression progressively increased during osteogenic differentiation of BMSCs. RAB7 knockdown impaired osteogenesis, whereas its overexpression enhanced the process. Functional assays demonstrated that modulation of RAB7 expression significantly influenced the effects of CREG1 on BMSCs. RAB7 knockdown inhibited CREG1-induced osteogenic differentiation and autophagy activation, whereas RAB7 overexpression restored the osteogenic potential suppressed by CREG1 knockdown. Our findings suggest that CREG1 facilitates osteogenic differentiation and bone homeostasis via RAB7-mediated regulation of autophagy.