Runx2-flox Mouse

Runx2, also known as Runt-related transcription factor 2, is a crucial transcription factor for skeletal development. It is expressed in multipotent mesenchymal cells, osteoblast-lineage cells, and chondrocytes. Runx2 plays a major role in chondrocyte maturation, osteoblast differentiation, and osteoprogenitor proliferation. It regulates chondrocyte proliferation by directly regulating Ihh expression and is involved in determining the type of cartilage formed. Runx2 also functions in multiple signaling pathways such as hedgehog, Fgf, Wnt, and Pthlh, which are important for the commitment of mesenchymal cells to osteoblast-lineage cells [2,4].

In the context of diseases, SIRT6-transgenic (SIRT6-Tg) mice showed alleviated vascular calcification (VC), while vascular smooth muscle cell-specific (VSMC-specific) SIRT6 knocked-down mice showed severe VC in chronic kidney disease. SIRT6 suppressed the osteogenic transdifferentiation of VSMCs via regulation of Runx2. SIRT6 bound to Runx2, deacetylated it, promoted its nuclear export, and subsequent degradation through the ubiquitin-proteasome system [1]. Also, in the study of cardiac remodeling, Alox5 deficiency significantly ameliorated transverse aortic constriction (TAC)-induced hypertrophy. Alox5 could bind to Runx2, promote its nuclear localization, and contribute to its liquid-liquid phase separation in the nucleus, increasing the transcription of EGFR in cardiomyocytes. Runx2 depletion alleviated hypertrophy in Ang II-pretreated Alox5-overexpressing cardiomyocytes [3].

In conclusion, Runx2 is essential for skeletal development, regulating chondrocyte and osteoblast-lineage cell processes. The gene knockout and conditional knockout mouse models have revealed its role in diseases like vascular calcification and cardiac remodeling. Understanding Runx2 provides insights into the mechanisms of bone-related and certain cardiovascular diseases, which may help in developing new therapeutic strategies [1,3].