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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
TRAIL effect on osteoclast formation in physiological and pathological conditions
Giacomina Brunetti1, Angela Oranger, Giorgio Mori
1Department of Human Anatomy and Histology, University of Bari, Bari, Italy.
Frontiers in Bioscience (Elite Edition)
|May 31, 2011
Summary
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) influences osteoclast formation differently in healthy individuals and patients with bone diseases. TRAIL can promote osteoclastogenesis independently or inhibit it when combined with RANKL.
Area of Science:
- Immunology
- Cell Biology
- Bone Biology
Background:
- Osteoclast (OC) differentiation is primarily regulated by the RANK/RANKL/OPG system.
- Inflammatory cytokines can influence osteoclastogenesis, contributing to bone loss in various diseases.
- Emerging evidence suggests Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) plays a role in modulating osteoclast formation.
Purpose of the Study:
- To investigate the dual role of TRAIL in osteoclast formation under physiological and pathological conditions.
- To elucidate TRAIL's impact on osteoclastogenesis in vitro using peripheral blood mononuclear cells (PBMCs) from healthy donors and patients with multiple myeloma or periodontal disease.
Main Methods:
- Utilized in vitro osteoclastogenesis models with PBMCs from healthy donors and patients.
- Assessed the effect of TRAIL alone and in combination with RANKL on osteoclast formation.
- Investigated the impact of TRAIL neutralization in patient-derived PBMCs.
- Measured TRAIL, RANKL, and OPG levels in patient sera.
Main Results:
- In healthy PBMCs, TRAIL induced osteoclast formation independently of RANKL but inhibited it when added with RANKL.
- In patient PBMCs (multiple myeloma, periodontal disease), TRAIL neutralization partially inhibited osteoclast formation, an effect reversed by RANKL.
- Elevated TRAIL, RANKL, and OPG levels were observed in patient PBMCs.
- High TRAIL levels were detected in the sera of patients.
Conclusions:
- TRAIL exhibits distinct roles in modulating osteoclast differentiation depending on the physiological or pathological context.
- These findings suggest TRAIL's complex involvement in bone metabolism and diseases characterized by bone loss.
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