Histochemical evidence of IGF2 mRNA-binding protein 2-mediated regulation of osteoclast function and adhesive ability

Insulin-like growth factor 2 (IGF2) messenger RNA-binding proteins (IMPs) are a family of oncofetal RNA-binding proteins that play important roles in cell migration, renewal, and metabolism. IMP2 gene expression may be important in determining IGF2 levels and might, thereby, be central to bone metabolism. In our present study, IMP2-deficient mice exhibited more immature bone structures, characterized by abundant residual cartilage cores; growth plates containing more rich cartilage matrix, which was arranged irregularly; and a significantly thicker hypertrophic chondrocyte layer in the femoral metaphysis, compared with wild-type mice. These abnormalities were associated with profound effects on the size and morphology of osteoclasts. Specifically, the osteoclasts exhibited various polymorphisms, failed to form resorption lacunae, and were detached from the bone surface. Consistent with these findings, IMP2 deficiency reduced the expression of two important proteases (cathepsin K and matrix metallopeptidase 9) as well as that of C-SRC, a critical regulator of ruffled border formation in osteoclasts, indicating impaired osteoclastic activity. IMP2-deficient mice also displayed inhibited osteoclast adhesion owing to defects in the CD44-osteopontin signaling pathway. In summary, we used IMP2-deficient mice as a model to determine whether IMP2 plays a role during bone metabolism. Our results indicate that IMP2 deficiency delayed bone remodeling by significantly inhibiting the activity of osteoclasts and impairing their adhesion.