Different Requirements of CBFB and RUNX2 in Skeletal Development among Calvaria, Limbs, Vertebrae and Ribs

RUNX proteins, such as RUNX2, regulate the proliferation and differentiation of chondrocytes and osteoblasts. Haploinsufficiency of RUNX2 causes cleidocranial dysplasia, but a detailed analysis of Runx2^+/- mice has not been reported. Furthermore, CBFB is required for the stability and DNA binding of RUNX family proteins. CBFB has two isoforms, and CBFB2 plays a major role in skeletal development. The calvaria, femurs, vertebrae and ribs in Cbfb2^-/- mice were analyzed after birth, and compared with those in Runx2^+/- mice. Calvarial development was impaired in Runx2^+/- mice but mildly delayed in Cbfb2^-/- mice. In femurs, the cortical bone but not trabecular bone was reduced in Cbfb2^-/- mice, whereas both the trabecular and cortical bone were reduced in Runx2^+/- mice. The trabecular bone in vertebrae increased in Cbfb2^-/- mice but not in Runx2^+/- mice. Rib development was impaired in Cbfb2^-/- mice but not in Runx2^+/- mice. These differences were likely caused by differences in the indispensability of CBFB and RUNX2, the balance of bone formation and resorption, or the number and maturation stage of osteoblasts. Thus, different amounts of CBFB and RUNX2 were required among the bone tissues for proper bone development and maintenance.