NF-κB decoy oligodeoxynucleotide enhanced osteogenesis in mesenchymal stem cells exposed to polyethylene particle

Tzu Hua Lin, Taishi Sato, Katherine R. Barcay, Heather Waters, Florence Loi, Ruth Zhang, Jukka Pajarinen, Kensuke Egashira, Zhenyu Yao, Stuart B. Goodman

Research output: Contribution to journalArticle

18 Citations (Scopus)

Abstract

Excessive generation of wear particles after total joint replacement may lead to local inflammation and periprosthetic osteolysis. Modulation of the key transcription factor NF-κB in immune cells could potentially mitigate the osteolytic process. We previously showed that local delivery of ultrahigh-molecular-weight polyethylene (UHMWPE) particles recruited osteoprogenitor cells and reduced osteolysis. However, the biological effects of modulating the NF-κB signaling pathway on osteoprogenitor/mesenchymal stem cells (MSCs) remain unclear. Here we showed that decoy oligodeoxynucleotide (ODN) increased cell viability when primary murine MSCs were exposed to UHMWPE particles, but had no effects on cellular apoptosis. Decoy ODN increased transforming growth factor-beta 1 (TGF-β1) and osteoprotegerin (OPG) in MSCs exposed to UHMWPE particles. Mechanistic studies showed that decoy ODN upregulated OPG expression through a TGF-β1-dependent pathway. By measuring the alkaline phosphatase activity, osteocalcin levels, Runx2 and osteopontin expression, and performing a bone mineralization assay, we found that decoy ODN increased MSC osteogenic ability when the cells were exposed to UHMWPE particles. Furthermore, the cellular response to decoy ODN and UHMWPE particles with regard to cell phenotype, cell viability, and osteogenic ability was confirmed using primary human MSCs. Our results suggest that modulation of wear particle-induced inflammation by NF-κB decoy ODN had no adverse effects on MSCs and may potentially further mitigate periprosthetic osteolysis by protecting MSC viability and osteogenic ability.

Original languageEnglish
Pages (from-to)875-883
Number of pages9
JournalTissue Engineering - Part A
Volume21
Issue number5-6
DOIs
Publication statusPublished - Mar 1 2015

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Oligodeoxyribonucleotides
Polyethylene
Stem cells
Mesenchymal Stromal Cells
Osteogenesis
Polyethylenes
Ultrahigh molecular weight polyethylenes
Osteolysis
Osteoprotegerin
Cell Survival
Transforming Growth Factor beta
Replacement Arthroplasties
Cells
Modulation
Wear of materials
Inflammation
Physiologic Calcification
Osteopontin
Transcription factors
Osteocalcin

All Science Journal Classification (ASJC) codes

  • Bioengineering
  • Biochemistry
  • Biomaterials
  • Biomedical Engineering

Cite this

NF-κB decoy oligodeoxynucleotide enhanced osteogenesis in mesenchymal stem cells exposed to polyethylene particle. / Lin, Tzu Hua; Sato, Taishi; Barcay, Katherine R.; Waters, Heather; Loi, Florence; Zhang, Ruth; Pajarinen, Jukka; Egashira, Kensuke; Yao, Zhenyu; Goodman, Stuart B.

In: Tissue Engineering - Part A, Vol. 21, No. 5-6, 01.03.2015, p. 875-883.

Research output: Contribution to journalArticle

Lin, TH, Sato, T, Barcay, KR, Waters, H, Loi, F, Zhang, R, Pajarinen, J, Egashira, K, Yao, Z & Goodman, SB 2015, 'NF-κB decoy oligodeoxynucleotide enhanced osteogenesis in mesenchymal stem cells exposed to polyethylene particle', Tissue Engineering - Part A, vol. 21, no. 5-6, pp. 875-883. https://doi.org/10.1089/ten.tea.2014.0144
Lin, Tzu Hua ; Sato, Taishi ; Barcay, Katherine R. ; Waters, Heather ; Loi, Florence ; Zhang, Ruth ; Pajarinen, Jukka ; Egashira, Kensuke ; Yao, Zhenyu ; Goodman, Stuart B. / NF-κB decoy oligodeoxynucleotide enhanced osteogenesis in mesenchymal stem cells exposed to polyethylene particle. In: Tissue Engineering - Part A. 2015 ; Vol. 21, No. 5-6. pp. 875-883.
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