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06:17
Osteoclast Derivation from Mouse Bone Marrow
Published on: November 6, 2014
Apoptotic osteocytes regulate osteoclast precursor recruitment and differentiation in vitro
Saja A Al-Dujaili1, Esther Lau, Hashem Al-Dujaili
1Institute of Biomaterials and Biomedical Engineering, University of Toronto, Toronto, ON, Canada.
Journal of Cellular Biochemistry
|May 4, 2011
Summary
Apoptotic osteocytes release factors that promote osteoclast formation and bone resorption. These findings reveal a mechanism where osteocyte apoptosis drives targeted bone remodeling by regulating osteoclast activity.
Area of Science:
- Bone Biology
- Cellular and Molecular Biology
- Skeletal Physiology
Background:
- Fatigue loading induces osteocyte apoptosis, which is spatially associated with bone resorption and microdamage.
- Osteocytes are known to influence osteoclastogenesis, suggesting a role for apoptosis in regulating bone remodeling.
Purpose of the Study:
- To investigate the hypothesis that osteocyte apoptosis regulates osteoclastogenesis.
- To determine the effect of soluble factors from apoptotic osteocytes on osteoclast precursor migration and differentiation.
Main Methods:
- Serum-starvation induced apoptosis in MLO-Y4 osteocyte-like cells.
- Conditioned media from apoptotic osteocytes (aOCY) and apoptosis-conditioned medium-treated osteocytes (atOCY) were used to treat osteoclast precursors (RAW264.7).
- Osteoclast precursor migration, differentiation, and gene/protein expression (RANKL, M-CSF, VEGF, OPG) were assessed.
Main Results:
- Soluble factors from aOCY and atOCY significantly increased osteoclast precursor migration and formation.
- Osteoclast size was also increased by aOCY and atOCY conditioned media.
- RANKL was upregulated by aOCY, while M-CSF and VEGF were increased by atOCY, with blocking antibodies confirming their roles.
Conclusions:
- Apoptotic osteocytes directly and indirectly initiate targeted bone resorption.
- Osteocyte apoptosis regulates osteoclast precursor recruitment and differentiation through specific molecular pathways (RANKL, M-CSF, VEGF).
- This study elucidates a critical mechanism linking bone microdamage, osteocyte apoptosis, and subsequent bone remodeling.
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