Gene Expression in Osteolysis: Review on the Identification of Altered Molecular Pathways in Preclinical and Clinical Studies

Abstract

Aseptic loosening (AL) due to osteolysis is the primary cause of joint prosthesis failure. Currently, a second surgery is still the only available treatment for AL, with its associated drawbacks. The present review aims at identifying genes whose expression is altered in osteolysis, and that could be the target of new pharmacological treatments, with the goal of replacing surgery. This review also aims at identifying the molecular pathways altered by different wear particles. We reviewed preclinical and clinical studies from 2010 to 2016, analyzing gene expression of tissues or cells affected by osteolysis. A total of 32 in vitro, 16 in vivo and six clinical studies were included. These studies revealed that genes belonging to both inflammation and osteoclastogenesis pathways are mainly involved in osteolysis. More precisely, an increase in genes encoding for the following factors were observed: Interleukins 6 and 1β (IL16 and β), Tumor Necrosis Factor α (TNFα), nuclear factor kappa-light-chain-enhancer of activated B cells (NFκB), Nuclear factor of activated T-cells, cytoplasmic 1 (NFATC1), Cathepsin K (CATK) and Tartrate-resistant acid phosphatase (TRAP). Titanium (Ti) and Polyethylene (PE) were the most studied particles, showing that Ti up-regulated inflammation and osteoclastogenesis related genes, while PE up-regulated primarily osteoclastogenesis related genes.

Keywords: aseptic loosening; gene expression; genomics; inflammation; osteoclastogenesis; osteolysis.

Figure 1

Search strategy of the review.

Figure 2

In vitro, in vivo and clinical studies dealing with different types of wear particles. The abscissa axis indicates the type of particles, while the ordinate axis indicates the number of studies dealing with each type of particles.