RelA promotes proliferation but inhibits osteogenic and chondrogenic differentiation of mesenchymal stem cells.

NF-κB is known to be implicated in skeletal development and related diseases. Previous studies have shown that RelA, a key subunit of NF-κB, is involved in osteoblast and chondrocyte survival and differentiation. Yet, the physiological roles of RelA in mesenchymal stem cells (MSCs), which give rise to both chondrocytes and osteoblasts, are still poorly understood. Here, we generated Prrx1-Cre;RelAf/f mice to delete RelA in Prrx1+ bone marrow MSCs and found that RelA deletion led to decreased MSC proliferation and altered differentiation, with increased osteogenic and chondrogenic differentiation but decreased adipogenic differentiation. Bone size and mass were not significantly changed in the mutant mice, although they developed moderate osteoarthritis-like phenotypes. Thus, our studies reveal important but discordant functions of RelA in MSC proliferation and differentiation, and provide an explanation why MSC-specific RelA knockout mice only develop minor skeletal phenotypes.