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Cell and Tissue Research

, Volume 358, Issue 1, pp 135–147 | Cite as

Deletion of Alox5 gene decreases osteogenic differentiation but increases adipogenic differentiation of mouse induced pluripotent stem cells

  • Yanru Wu
  • Hualing Sun
  • Fangfang Song
  • Cui Huang
  • Jiawei WangEmail author
Regular Article

Abstract

Induced pluripotent stem cells (iPSCs) have great potential in bone tissue engineering to repair large bone defects. Before their clinical application, investigations are needed to discover the genes and osteoconductive scaffolds that influence their differentiation toward an osteogenic lineage. Alox5 plays controversial and complex roles in the regulation of bone and fat metabolism. To detect the effect of Alox5 on osteogenic and adipogenic differentiation of iPSCs, both Alox5 knockout mouse iPSCs (Alox5-KO-iPSCs) and wild-type mouse iPSCs (Wild-iPSCs) were developed. The mRNA levels of many osteogenic markers in Alox5-KO-iPSCs were significantly reduced, while many adipogenic markers were enhanced. Furthermore, when implanted in rat cranial critical-sized defects with collagen/chitosan/hydroxyapatite scaffolds (CCHS), Alox5-KO-iPSCs produced significantly less new bone than Wild-iPSCs and both cell-scaffold groups had no tumor formation. There was a significant difference in the expression of Cox2 during the osteogenic and adipogenic differentiation between the two kinds of iPSCs in vitro. In conclusion, firstly, Alox5 knockout reduced the osteogenic but increased the adipogenic differentiation potential of mouse iPSCs. These disorders might be related to the change of Cox2 expression. Secondly, combined with iPSCs, CCHS can serve as a potential substrate to repair critical-sized bony defects. However, more studies are required to confirm the mechanisms through which Alox5 affects the osteogenic and adipogenic abilities of iPSCs in vivo and the effect of Cox2 inhibition in this system.

Keywords

Alox5 iPSCs Collagen/chitosan/hydroxyapatite scaffolds Bone regeneration Calvarial defects 

Notes

Acknowledgement

This work was financially supported by The Fundamental Research Fund for the Central Universities of China (2012304020207) and a grant from The Office of Science and Technology of Hubei Province (2011CDB470).

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Copyright information

© Springer-Verlag Berlin Heidelberg 2014

Authors and Affiliations

  • Yanru Wu
    • 1
  • Hualing Sun
    • 1
  • Fangfang Song
    • 1
  • Cui Huang
    • 1
  • Jiawei Wang
    • 1
    Email author
  1. 1.Breeding Base of Basic Science of Stomatology (Hubei-MOST) & Key Laboratory of Oral Biomedicine Ministry of Education School & Hospital of StomatologyWuhan UniversityWuhanPeople’s Republic of China

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