Silence of Linc01152 promotes chondrogenic differentiation and facilitates cartilage repair through directly increasing SOX9 expression

The long intergenic non-coding RNA Linc01152 is a recently identified lncRNA whose functional involvement in osteoarthritis (OA) remains largely understood. In the present study, we tried to elucidate the role of Linc01152 in chondrogenic differentiation of human mesenchymal stem cells (hMSCs), as well as to investigate its potential contribution to cartilage regeneration during the progression of OA. Linc01152 was identified on the antisense strand of SOX9 through bioinformatic analyses; its expression exhibited significant correlation with SOX9 in clinical specimens and during hMSCs chondrogenesis. The Linc01152-modulated hMSCs were subjected to chondrogenic induction, and the effects were evaluated by Alcian Blue/Safranin O staining and chondrogenesis-related genes expression analysis. A cartilage defect model was established, and cartilage repair was examined by micro-CT, Safranin O/Fast Green staining, and immunohistochemistry staining. The NF-κB signaling was evaluated using RNA-sequencing, RT-PCR, luciferase reporter assays, and Western blotting analysis. Our results revealed an inverse correlation between Linc01152 and SOX9 expression in clinical samples (Y = -37.29X + 22.91, r = -0.3435, p = 0.0146), which was recapitulated during chondrogenic differentiation of hMSCs. Linc01152 knockdown promoted chondrogenic differentiation, whereas its overexpression suppressed this differentiation. Notably, Linc01152 silenced hMSCs significantly accelerated cartilage defect repair in a nude mouse model. Furthermore, activation of NF-κB signaling was validated to play a pivotal role in Linc01152-mediated chondrogenesis. Linc01152 knockdown promoted chondrogenic differentiation of hMSCs in vitro and contributed to cartilage formation in vivo through negatively regulated SOX9 expression and activation of the NF-κB signaling pathway. The original data presented in the study are included in the article/supplementary material, further inquiries can be directed to the corresponding authors.