Histochemical evidence of IGF2 mRNA-binding protein 2-mediated regulation of osteoclast function and adhesive ability
- 110 Downloads
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.
KeywordsIMP2 Bone remodeling Osteoclast Adhesion
We thank Liwen Bianji, Edanz Editing China (http://www.liwenbianji.cn/ac), for editing the English text of a draft of this manuscript.
Compliance with ethical standards
Conflict of interest
The authors declare that they have no conflict of interest.
- Barghash A, Golob-Schwarzl N, Helms V, Haybaeck J, Kessler SM (2016) Elevated expression of the IGF2 mRNA binding protein 2 (IGF2BP2/IMP2) is linked to short survival and metastasis in esophageal adenocarcinoma. Oncotarget 7:49743–49750. https://doi.org/10.18632/oncotarget.10439 CrossRefPubMedPubMedCentralGoogle Scholar
- Kessler SM, Pokorny J, Zimmer V, Laggai S, Lammert F, Bohle RM, Kiemer AK (2013) IGF2 mRNA binding protein p62/IMP2–2 in hepatocellular carcinoma: antiapoptotic action is independent of IGF2/PI3K signaling. Am J Physiol Gastrointest Liver Physiol 304:G328-336. https://doi.org/10.1152/ajpgi.00005.2012 CrossRefGoogle Scholar
- Schaeffer V, Hansen KM, Morris DR, LeBoeuf RC, Abrass CK (2012) RNA-binding protein IGF2BP2/IMP2 is required for laminin-beta2 mRNA translation and is modulated by glucose concentration. Am J Physiol Renal Physiol 303:F75–F82. https://doi.org/10.1152/ajprenal.00185.2012 CrossRefPubMedPubMedCentralGoogle Scholar
- Suzuki K, Zhu B, Rittling SR, Denhardt DT, Goldberg HA, McCulloch CA, Sodek J (2002) Colocalization of intracellular osteopontin with CD44 is associated with migration, cell fusion, and resorption in osteoclasts. J Bone Miner Res 17:1486–1497. https://doi.org/10.1359/jbmr.2002.17.8.1486 CrossRefPubMedGoogle Scholar
- Zhou SL et al (2014) Autoantibody detection to tumor-associated antigens of P53, IMP1, P16, cyclin B1, P62, C-myc, Survivn, and Koc for the screening of high-risk subjects and early detection of esophageal squamous cell carcinoma. Dis Esophagus 27:790–797. https://doi.org/10.1111/dote.12145 CrossRefPubMedGoogle Scholar