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Epidermal growth factor receptor regulates osteoclast differentiation and survival through cross-talking with RANK signaling.
J Cell Physiol. 2008 Nov; 217(2):409-22.JC

Abstract

The epidermal growth factor receptor (EGFR) functions in various cellular physiological processes such as proliferation, differentiation, and motility. Although recent studies have reported that EGFR signaling is involved in osteoclast recruitment and formation, the molecular mechanism of EGFR signaling for the regulation of osteoclastogenesis remains unclear. We investigated the role of the EGFR in osteoclast differentiation and survival and show that the expression of the EGFR was highly up-regulated by receptor activator of nuclear factor-kappaB ligand (RANKL) during osteoclast differentiation. EGFR-specific tyrosine kinase inhibitors and EGFR knockdown blocked RANKL-dependent osteoclast formation, suggesting that EGFR signaling plays an important role in osteoclastogenesis. EGFR inhibition impaired the RANKL-mediated activation of osteoclastogenic signaling pathways, including c-Jun N-terminal kinase (JNK), NF-kappaB, and Akt/protein kinase B (PKB). In addition, EGFR inhibition in differentiated osteoclasts caused apoptosis through caspase activation. Inhibition of the phosphoinositide-3 kinase (PI3K)-Akt/PKB pathway and subsequent activation of BAD and caspases-9 and -3 may be responsible for the EGFR inhibition-induced apoptosis. The EGFR physically associated with receptor activator of nuclear factor-kappaB (RANK) and Grb2-associated binder 2 (Gab2). Moreover, RANKL transactivated EGFR. These data indicate that EGFR regulates RANKL-activated signaling pathways by cross-talking with RANK, suggesting that the EGFR may play a crucial role as a RANK downstream signal and/or a novel type of RANK co-receptor in osteoclast differentiation and survival.

Authors+Show Affiliations

Department of Cell and Developmental Biology, School of Dentistry and Dental Research Institute, Seoul National University, Seoul, Republic of Korea.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

18543257

Citation

Yi, Tacghee, et al. "Epidermal Growth Factor Receptor Regulates Osteoclast Differentiation and Survival Through Cross-talking With RANK Signaling." Journal of Cellular Physiology, vol. 217, no. 2, 2008, pp. 409-22.
Yi T, Lee HL, Cha JH, et al. Epidermal growth factor receptor regulates osteoclast differentiation and survival through cross-talking with RANK signaling. J Cell Physiol. 2008;217(2):409-22.
Yi, T., Lee, H. L., Cha, J. H., Ko, S. I., Kim, H. J., Shin, H. I., Woo, K. M., Ryoo, H. M., Kim, G. S., & Baek, J. H. (2008). Epidermal growth factor receptor regulates osteoclast differentiation and survival through cross-talking with RANK signaling. Journal of Cellular Physiology, 217(2), 409-22. https://doi.org/10.1002/jcp.21511
Yi T, et al. Epidermal Growth Factor Receptor Regulates Osteoclast Differentiation and Survival Through Cross-talking With RANK Signaling. J Cell Physiol. 2008;217(2):409-22. PubMed PMID: 18543257.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Epidermal growth factor receptor regulates osteoclast differentiation and survival through cross-talking with RANK signaling. AU - Yi,Tacghee, AU - Lee,Hye-Lim, AU - Cha,Ji-Hoon, AU - Ko,Soo-Il, AU - Kim,Hye-Jin, AU - Shin,Hong-In, AU - Woo,Kyung-Mi, AU - Ryoo,Hyun-Mo, AU - Kim,Gwan-Shik, AU - Baek,Jeong-Hwa, PY - 2008/6/11/pubmed PY - 2008/9/16/medline PY - 2008/6/11/entrez SP - 409 EP - 22 JF - Journal of cellular physiology JO - J Cell Physiol VL - 217 IS - 2 N2 - The epidermal growth factor receptor (EGFR) functions in various cellular physiological processes such as proliferation, differentiation, and motility. Although recent studies have reported that EGFR signaling is involved in osteoclast recruitment and formation, the molecular mechanism of EGFR signaling for the regulation of osteoclastogenesis remains unclear. We investigated the role of the EGFR in osteoclast differentiation and survival and show that the expression of the EGFR was highly up-regulated by receptor activator of nuclear factor-kappaB ligand (RANKL) during osteoclast differentiation. EGFR-specific tyrosine kinase inhibitors and EGFR knockdown blocked RANKL-dependent osteoclast formation, suggesting that EGFR signaling plays an important role in osteoclastogenesis. EGFR inhibition impaired the RANKL-mediated activation of osteoclastogenic signaling pathways, including c-Jun N-terminal kinase (JNK), NF-kappaB, and Akt/protein kinase B (PKB). In addition, EGFR inhibition in differentiated osteoclasts caused apoptosis through caspase activation. Inhibition of the phosphoinositide-3 kinase (PI3K)-Akt/PKB pathway and subsequent activation of BAD and caspases-9 and -3 may be responsible for the EGFR inhibition-induced apoptosis. The EGFR physically associated with receptor activator of nuclear factor-kappaB (RANK) and Grb2-associated binder 2 (Gab2). Moreover, RANKL transactivated EGFR. These data indicate that EGFR regulates RANKL-activated signaling pathways by cross-talking with RANK, suggesting that the EGFR may play a crucial role as a RANK downstream signal and/or a novel type of RANK co-receptor in osteoclast differentiation and survival. SN - 1097-4652 UR - https://www.unboundmedicine.com/medline/citation/18543257/Epidermal_growth_factor_receptor_regulates_osteoclast_differentiation_and_survival_through_cross_talking_with_RANK_signaling_ L2 - https://doi.org/10.1002/jcp.21511 DB - PRIME DP - Unbound Medicine ER -