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Is HMGB1 an osteocyte alarmin?
Joseph P Bidwell1, Jieping Yang, Alexander G Robling
1Department of Anatomy and Cell Biology, Indiana University School of Medicine, Indianapolis, Indiana 46202, USA. jbidwell@iupui.edu
Journal of Cellular Biochemistry
|October 24, 2007
Summary
Osteocyte death signals bone repair and loss. High mobility group box 1 protein (HMGB1) acts as an osteocyte alarmin, mediating bone remodeling and inflammatory bone loss.
Area of Science:
- Bone Biology
- Immunology
- Cell Death
Background:
- Osteocyte apoptosis is crucial for bone resorption and remodeling.
- Osteocyte death may signal osteoclast development and migration to damaged bone sites.
- This process is implicated in bone repair and inflammatory bone loss.
Purpose of the Study:
- To review the role of high mobility group box 1 protein (HMGB1) at the immune-bone interface.
- To propose HMGB1 as an osteocyte alarmin.
- To elucidate HMGB1's role in normal bone remodeling and inflammatory bone loss.
Main Methods:
- Review of existing literature on HMGB1 and bone biology.
- Analysis of studies showing HMGB1 release from apoptotic osteoblasts (MLO-Y4 cells).
- Examination of HMGB1's effects on osteoblastogenic stromal cells and osteoclast chemotaxis.
Main Results:
- HMGB1 is released by apoptotic osteoblasts and osteocyte-like cells.
- Extracellular HMGB1 enhances RANKL, TNFalpha, and IL6 expression in bone marrow stromal cells.
- HMGB1 exhibits chemotactic activity towards osteoclasts.
Conclusions:
- HMGB1 functions as a bone-active cytokine and an "alarmin" for osteocytes.
- HMGB1 plays a significant role in mediating normal bone remodeling.
- HMGB1 is implicated in the pathogenesis of inflammatory bone loss.
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