Epidermal growth factor receptor plays an anabolic role in bone metabolism in vivo

Xianrong Zhang, Joseph Tamasi, Xin Lu, Ji Zhu, Haiyan Chen, Xiaoyan Tian, Tang Cheng Lee, David W. Threadgill, Barbara E. Kream, Yibin Kang, Nicola Partridge, Ling Qin

Research output: Contribution to journalArticle

Abstract

While the epidermal growth factor receptor (EGFR)-mediated signaling pathway has been shown to have vital roles in many developmental and pathologic processes, its functions in the development and homeostasis of the skeletal system has been poorly defined. To address its in vivo role, we constructed transgenic and pharmacologic mouse models and used peripheral quantitative computed tomography (pQCT), micro-computed tomography (ÂμCT) and histomorphometry to analyze their trabecular and cortical bone phenotypes. We initially deleted the EGFR in preosteoblasts/osteoblasts using a Cre/loxP system (Col-Cre Egfrf/f), but no bone phenotype was observed because of incomplete deletion of the Egfr genomic locus. To further reduce the remaining osteoblastic EGFR activity, we introduced an EGFR dominant-negative allele, Wa5, and generated Col-Cre EgfrWa5/f mice. At 3 and 7 months of age, both male and female mice exhibited a remarkable decrease in tibial trabecular bone mass with abnormalities in trabecular number and thickness. Histologic analyses revealed decreases in osteoblast number and mineralization activity and an increase in osteoclast number. Significant increases in trabecular pattern factor and structural model index indicate that trabecular microarchitecture was altered. The femurs of these mice were shorter and smaller with reduced cortical area and periosteal perimeter. Moreover, colony-forming unit-fibroblast (CFU-F) assay indicates that these mice had fewer bone marrow mesenchymal stem cells and committed progenitors. Similarly, administration of an EGFR inhibitor into wild-type mice caused a significant reduction in trabecular bone volume. In contrast, EgfrDsk5/+ mice with a constitutively active EGFR allele displayed increases in trabecular and cortical bone content. Taken together, these data demonstrate that the EGFR signaling pathway is an important bone regulator and that it primarily plays an anabolic role in bone metabolism.

Original languageEnglish (US)
Pages (from-to)1022-1034
Number of pages13
JournalJournal of Bone and Mineral Research
Volume26
Issue number5
DOIs
StatePublished - May 2011

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Epidermal Growth Factor Receptor
Bone and Bones
Osteoblasts
Alleles
Tomography
Colony-Forming Units Assay
Phenotype
Structural Models
Osteoclasts
Pathologic Processes
Mesenchymal Stromal Cells
Femur
Transgenic Mice
Homeostasis
Fibroblasts
Bone Marrow
Cancellous Bone

Keywords

  • ANIMAL MODELS
  • BONE MASS
  • EPIDERMAL GROWTH FACTOR RECEPTOR
  • OSTEOBLAST
  • SKELETAL PHENOTYPE

ASJC Scopus subject areas

  • Orthopedics and Sports Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Zhang, X., Tamasi, J., Lu, X., Zhu, J., Chen, H., Tian, X., ... Qin, L. (2011). Epidermal growth factor receptor plays an anabolic role in bone metabolism in vivo. Journal of Bone and Mineral Research, 26(5), 1022-1034. https://doi.org/10.1002/jbmr.295

Epidermal growth factor receptor plays an anabolic role in bone metabolism in vivo. / Zhang, Xianrong; Tamasi, Joseph; Lu, Xin; Zhu, Ji; Chen, Haiyan; Tian, Xiaoyan; Lee, Tang Cheng; Threadgill, David W.; Kream, Barbara E.; Kang, Yibin; Partridge, Nicola; Qin, Ling.

In: Journal of Bone and Mineral Research, Vol. 26, No. 5, 05.2011, p. 1022-1034.

Research output: Contribution to journalArticle

Zhang, X, Tamasi, J, Lu, X, Zhu, J, Chen, H, Tian, X, Lee, TC, Threadgill, DW, Kream, BE, Kang, Y, Partridge, N & Qin, L 2011, 'Epidermal growth factor receptor plays an anabolic role in bone metabolism in vivo', Journal of Bone and Mineral Research, vol. 26, no. 5, pp. 1022-1034. https://doi.org/10.1002/jbmr.295
Zhang, Xianrong ; Tamasi, Joseph ; Lu, Xin ; Zhu, Ji ; Chen, Haiyan ; Tian, Xiaoyan ; Lee, Tang Cheng ; Threadgill, David W. ; Kream, Barbara E. ; Kang, Yibin ; Partridge, Nicola ; Qin, Ling. / Epidermal growth factor receptor plays an anabolic role in bone metabolism in vivo. In: Journal of Bone and Mineral Research. 2011 ; Vol. 26, No. 5. pp. 1022-1034.
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