Enhanced osteogenic differentiation of human mesenchymal stem cells by direct delivery of Cbfβ protein

Jaeyoung Lee, Hyeonjin Cha, Tai Hyun Park, Ju Hyun Park

Research output: Contribution to journalArticlepeer-review

6 Scopus citations

Abstract

Core binding factor β (Cbfβ) is a non-DNA binding cofactor of Runx2 that potentiates DNA binding. Previously, it has been reported that Cbfβ plays an essential role in osteogenic differentiation and skeletal development by inhibition adipogenesis. Here, we delivered the recombinant Cbfβ protein into human mesenchymal stem cells (MSCs) and triggered osteogenic lineage commitment. The efficient delivery of Cbfβ was achieved by fusing 30Kc19 protein, which is a cell-penetrating protein derived from the silkworm. After the production of the recombinant Cbfβ-30Kc19 protein in the Escherichia coli expression system, and confirmation of its intracellular delivery, MSCs were treated with the Cbfβ-30Kc19 once or twice up to 300 µg/ml. By investigating the upregulation of osteoblast-specific genes and phenotypical changes, such as calcium mineralization, we demonstrated that Cbfβ-30Kc19 efficiently induced osteogenic differentiation in MSCs. At the same time, Cbfβ-30Kc19 suppressed adipocyte formation and downregulated the expression of adipocyte-specific genes. Our results demonstrate that the intracellularly delivered Cbfβ-30Kc19 enhances osteogenesis in MSCs, whereas it suppresses adipogenesis by altering the transcriptional regulatory network involved in osteoblast-adipocyte lineage commitment. Cbfβ-30Kc19 holds great potential for the treatment of bone-related diseases, such as osteoporosis, by allowing transcriptional regulation in MSCs, and overcoming the limitations of current therapies.

Original languageEnglish
Pages (from-to)2897-2910
Number of pages14
JournalBiotechnology and Bioengineering
Volume117
Issue number9
DOIs
StatePublished - 1 Sep 2020

Bibliographical note

Funding Information:
This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation funded by Korean Government (Ministry of Science and ICT) (Grant No. 2017M3A9C6031798).

Funding Information:
This research was supported by the Bio & Medical Technology Development Program of the National Research Foundation funded by Korean Government (Ministry of Science and ICT) (Grant No. 2017M3A9C6031798).

Publisher Copyright:
© 2020 Wiley Periodicals LLC

Keywords

  • Cbfβ
  • differentiation
  • intracellular delivery
  • mesenchymal stem cell
  • osteoblast

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