Small nucleolar RNA host genes (SNHGs), members of long-chain noncoding RNAs (lncRNAs), have received increasing attention regarding their roles in multiple bone diseases. Studies have revealed that SNHGs display unique expression profile during osteoblast differentiation and that they could act as promising biomarkers of certain bone diseases, such as osteoporosis. Osteogenesis of mesenchymal stem cells (MSCs) is an important part of bone repair and reconstruction. Moreover, studies confirmed that the SNHG family participate in the regulation of osteogenic differentiation of MSCs in part by regulating important pathways of osteogenesis, such as Wnt/β-catenin signaling. Based on these observations, clarifying the SNHG family’s roles in osteogenesis (especially in MSCs) and their related mechanisms would provide novel ideas for possible applications of lncRNAs in the diagnosis and treatment of bone diseases. After searching, screening, browsing and intensive reading, we uncovered more than 30 papers related to the SNHG family and osteoblast differentiation that were published in recent years. Here, our review aims to summarize these findings in order to provide a theoretical basis for further research.

Craniofacial bone defects induced by congenital malformations, trauma, or diseases frequently challenge the orthodontic or restorative treatment. Stem cell‐based bone regenerative approaches emerged as a promising method to resolve bone defects. Microenvironment physical cues, such as the matrix elastic modulus or matrix topography, regulate stem cell differentiation via multiple genes. We constructed gelatin methacryloyl (GelMA), a well‐known scaffold, to investigate the impact of elastic modulus on osteogenic differentiation in a three‐dimensional environment. Confocal microscope was used to observe and assess the condensates fission and fusion. New bone formation was evaluated by micro‐computed tomography at 6 weeks in calvarial defect rat. We found that the light curing increased elastic modulus of GelMA, and the pore size of GelMA decreased. The expression of osteogenic markers was inhibited in hBMSCs cultured in the low‐elastic‐modulus GelMA. In contrast, the expression of YAP, TAZ and TEAD was increased in the hBMSCs in the low‐elastic‐modulus GelMA. Furthermore, YAP assembled via liquid–liquid phase separation (LLPS) into condensates that were sensitive to 1′6‐hexanediol. YAP recruit TAZ and TEAD4, but not RUNX2 into the condensates. In vivo, we also found that hBMSCs in high‐elastic‐modulus GelMA was more apt to form new bone. This study provides new insight into the mechanism of osteogenic differentiation. Reagents that can regulate the elastic modulus of substrate or LLPS may be applied to promote bone regeneration.