Inhibition of Axin1 in osteoblast precursor cells leads to defects in postnatal bone growth through suppressing osteoclast formation

Axin1 is a negative regulator of beta-catenin signaling and its role in osteoblast precursor cells remains undefined. In the present studies, we determined changes in postnatal bone growth by deletion ofAxin1in osteoblast precursor cells and analyzed bone growth in newborn and postnatalAxin1(Osx)mice and found that hypertrophic cartilage area was largely expanded inAxin1(Osx)KO mice. A larger number of chondrocytes and unabsorbed cartilage matrix were found in the bone marrow cavity ofAxin1(Osx)KO mice. Osteoclast formation in metaphyseal and subchondral bone areas was significantly decreased, demonstrated by decreased TRAP-positive cell numbers, associated with reduction of MMP9- and cathepsin K-positive cell numbers inAxin1(Osx)KO mice. OPG expression and the ratio ofOpgtoRanklwere significantly increased in osteoblasts ofAxin1(Osx)KO mice. Osteoclast formation in primary bone marrow derived microphage (BMM) cells was significantly decreased when BMM cells were cultured with conditioned media (CM) collected from osteoblasts derived fromAxin1(Osx)mice compared with BMM cells cultured with CM derived from WT mice. Thus, the loss of Axin1 in osteoblast precursor cells caused increased OPG and the decrease in osteoclast formation, leading to delayed bone growth in postnatalAxin1(Osx)KO mice.