Abstract: Somatostatin （SST）is a multifunctional peptide and an important regulator of the endocrine growth axis, exerting a wide range of endocrine and exocrine functions. Scattered evidence suggested a possible role for SST in bone physiology. The aim of this study was to investigate the regulatory role of growth inhibitor signaling pathway in zebrafish skeletal development. The effects of SST signaling on skeletal development were assessed using ansst1. 2knockout zebrafish model and a combination of techniques, including Alisin blue cartilage staining, Alizarin red sclerosteum staining, micro-CT scanning, calcium xanthophyll labelling, and expression analysis of key osteogenic genes. The results showed thatsst1. 2deletion did not significantly affect cartilage development or intramembranous ossification of the spine, but significantly increased the bone mass of the zebrafish mutant skull. The development of scales was not affected. Histological analysis and osteogenic gene expression confirmed that the increased bone mass was due to enhanced endochondral ossification. These results suggested that SST signaling regulated bone mass by inhibiting endochondral ossification during zebrafish osteogenesis. The findings provided a new theoretical basis for a deeper understanding of skeletal development in fish and suggest new ideas for establishing more accurate models of skeletal dysplasia diseases, such as bone metabolic disorders.

Key words: somatostatin, bone mass, endochondral ossification, zebrafish, CRISPR/Cas9