TCF12, known as Transcription Factor 12, is a key regulator involved in various cell development and differentiation processes. It has been associated with multiple signaling pathways, such as TGF-β/Smad2/3, S1P/S1PR4/STAT3, and Notch1 signaling pathways, and is of great biological importance in different organs and diseases [1,2,3]. Genetic models, like KO/CKO mouse models, are valuable for studying its functions.

In osteoarthritis (OA), TCF12 expression is upregulated in chondrocytes stimulated with IL-1β and osteoarthritic chondrocytes. Knockdown of TCF12 in a mouse model generated by destabilization of the medial meniscus alleviated cartilage damage, indicating that TCF12 aggravates OA progression by targeting CXCR4 and activating the TGF-β signaling pathway [1]. In osteosarcoma, knockdown of TCF12 reduced the proliferation, migration, and invasion of osteosarcoma cells, suggesting its role in promoting the malignancy of osteosarcoma [2]. In breast cancer, TCF12 directly binds to the promoter of the GRB7 gene to promote its transcription, facilitating HER2 + breast cancer progression [3]. In glioblastoma, TCF12 deficiency severely impairs tumor cell proliferation in vitro by disrupting the G1 to S phase transition and significantly improves animal survival in vivo [4].

In conclusion, TCF12 plays crucial roles in cell development, differentiation, and disease processes, as revealed through model-based research. KO/CKO mouse models have contributed to understanding its roles in diseases like osteoarthritis, osteosarcoma, breast cancer, and glioblastoma, providing insights into potential therapeutic targets for these diseases.