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Updated: Mar 7, 2026
A Novel in vivo Gene Transfer Technique and in vitro Cell Based Assays for the Study of Bone Loss in Musculoskeletal Disorders
Published on: June 8, 2014
Gene Expression in Osteolysis: Review on the Identification of Altered Molecular Pathways in Preclinical and Clinical
Francesca Veronesi1, Matilde Tschon2, Milena Fini3
1Laboratory of Preclinical and Surgical Studies, Rizzoli Orthopedic Institute, via di Barbiano 1/10, 40136 Bologna, Italy. francesca.veronesi@ior.it.
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.
Insights
This review identifies key genes and molecular pathways involved in osteolysis, the main cause of joint replacement failure. Findings may lead to new drug treatments to avoid revision surgery.
Area of Science:
- Biomaterials Science
- Molecular Biology
- Orthopedic Surgery
Background:
- Aseptic loosening (AL) due to osteolysis is the primary cause of joint prosthesis failure, necessitating revision surgery.
- Current treatments for AL are limited to surgical intervention, which carries significant drawbacks.
- Identifying molecular targets for pharmacological intervention could offer a non-surgical alternative.
Purpose of the Study:
- To identify genes with altered expression in osteolysis.
- To pinpoint molecular pathways affected by wear particles from joint prostheses.
- To explore potential pharmacological targets for treating aseptic loosening and preventing prosthesis failure.
Main Methods:
- Systematic review of preclinical and clinical studies published between 2010 and 2016.
- Analysis of gene expression in tissues or cells affected by osteolysis.
- Inclusion of 32 in vitro, 16 in vivo, and 6 clinical studies.
Main Results:
- Osteolysis involves key genes in inflammation and osteoclastogenesis pathways.
- Increased expression of Interleukins (IL-6, IL-1β), TNFα, NFκB, NFATC1, Cathepsin K (CATK), and TRAP were observed.
- Titanium particles upregulated inflammation and osteoclastogenesis genes, while Polyethylene particles primarily upregulated osteoclastogenesis genes.
Conclusions:
- Genes related to inflammation and osteoclastogenesis are central to osteolysis.
- Specific molecular pathways and genes are differentially affected by Titanium and Polyethylene wear particles.
- Targeting these identified genes and pathways offers potential for novel pharmacological treatments for aseptic loosening.
