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-?B in immune cells could potentially mitigate the osteolytic process. We previously showed that local delivery of ultra-high molecular weight polyethylene (UHMWPE) particles recruited osteoprogenitor cells and reduced osteolysis. However, the biological effects of modulating the NF-?B 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 TGF-ß1 and osteoprotegerin in MSCs exposed to UHMWPE particles. Mechanistic studies showed that decoy ODN up-regulated osteoprotegerin expression through a TGF-ß1 dependent pathway. By measuring 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 regards to cell phenotype, cell viability and osteogenic ability were confirmed using primary human MSCs. Our results suggest that modulation of wear particle induced inflammation by NF-?B decoy ODN had no adverse effects on MSCs, and may potentially further mitigate peri-prosthetic osteolysis by protecting MSC viability and osteogenic ability.

View details for DOI 10.1089/ten.TEA.2014.0144

View details for PubMedID 25518013