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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
Beta2-microglobulin stimulates osteoclast formation.
C Menaa1, E Esser, S M Sprague
1Evanston Northwestern Healthcare and Northwestern University Feinberg School of Medicine, Evanston, Illinois 60201, USA.
Kidney International
|March 28, 2008
Summary
Beta-2 microglobulin (beta(2)M) directly stimulates osteoclast activity, causing bone destruction in dialysis-related amyloidosis. This process involves cytokine production and is linked to chronic kidney disease complications.
Area of Science:
- Nephrology
- Bone Biology
- Immunology
Background:
- Dialysis-related amyloidosis (DRA) is a complication of long-term chronic kidney disease (CKD).
- DRA involves beta-2 microglobulin (beta(2)M) amyloid deposition in osteoarticular tissues, leading to arthropathy, bone cysts, and fractures.
- Osteolytic lesions are characteristic findings in DRA.
Purpose of the Study:
- To investigate if beta(2)M directly stimulates osteoclast activity.
- To determine if local cytokine production mediates beta(2)M-induced bone destruction.
- To elucidate the role of beta(2)M in the pathogenesis of bone complications in CKD.
Main Methods:
- Cultured mouse marrow cells, colony-forming unit granulocyte macrophages, and RAW 264.7 monocytic cells were treated with beta(2)M.
- Osteoclastogenesis was assessed by counting tartrate-resistant alkaline phosphatase-positive multinucleated cells.
- Cytokine expression (TNF-alpha, IL-1) was measured, and the effect of a TNF-alpha-neutralizing antibody was evaluated.
Main Results:
- Beta-2 microglobulin (beta(2)M) induced a dose-dependent increase in osteoclast formation.
- Osteoclastogenesis occurred independently of osteoblasts or stromal cells.
- Beta(2)M upregulated TNF-alpha and IL-1 expression, and TNF-alpha neutralization blocked beta(2)M-induced osteoclast formation.
Conclusions:
- Beta-2 microglobulin (beta(2)M) directly stimulates osteoclastogenesis.
- Tumor necrosis factor-alpha (TNF-alpha) mediates the osteoclastogenic effect of beta(2)M.
- These findings support a direct role for beta(2)M in causing bone destruction in dialysis-related amyloidosis and CKD.
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