Osteoarthritis (OA) is a degenerative joint disorder which affects about 80% of the population above 65 years revealing radiographic evidence of OA. Recently, more and more researches have been conducted on the molecular mechanism of OA to find target treatments. RNA binding proteins (RBPs) play a key role in genome regulation. Nucleolar GTP-binding Protein 3 (GNL3) is abundantly expressed in bone marrow mesenchymal stem cells and correlates with chondrocytes differentiation. Here we report the transcriptome study of GNL3, which regulates transcription in osteoarthritis (OA). In this study, RNA sequencing (RNA-seq) was used to analyze the global transcription level in HeLa cells. The results showed that the expression of IL24 and PTN was down-regulated when GNL3 was knocked down. Likewise, in the lesions of osteoarthritis, the expression level of GNL3, IL24 and PTN gene were significantly up-regulated compared with the control group. IL24 contributes to the progression of osteoarthritis by inducing bone cells apoptosis at the joint, and PTN contributes to the progression of osteoarthritis by promoting angiogenesis. This study aimed to assess the association between GNL3 and both of these two downstream genes as a potential biomarker for investigating the development of OA.