Recent evidence suggests that adipokines are involved in the regulation of bone metabolism. Ctrp4 is a newly discovered member of the adipokine CTRP family. Studies have shown that Ctrp4 is involved in the regulation of tumor cell inflammatory signaling pathways and acts on the hypothalamus to regulate food intake, but its role in osteoblasts is not yet clear. In this study, we found that the expression of Ctrp4 in bone tissue was significantly decreased in the tail-suspended mouse, while that in ovariectomized-simulated osteoporosis mice decreased similarly, indicating that Ctrp4 was involved in osteogenesis regulation. We further isolated Alp-positive osteoblasts from the femur of tail-suspended rats and confirmed that the expression of Ctrp4, Bglap and Alp was down-regulated in the process of bone loss caused by tail suspension. In the process of inducing osteoblastic differentiation in vitro, Ctrp4 interfering significantly inhibited the expression of Alp and Bglap. In addition, inhibition of Ctrp4 resulted in decreased alkaline phosphatase expression and less alizarin red staining, indicating that Ctrp4 promoted osteogenic differentiation and osteoblasts mineralization. In conclusion, our results suggest that Ctrp4 is involved in bone metabolism regulation and promotes osteoblast differentiation, which may become a potential target for future intervention in bone metabolic diseases. (C) 2019 Elsevier Inc. All rights reserved.