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Low calcium environment effects osteoprotegerin ligand/osteoclast differentiation factor
S Takeyama1, Y Yoshimura, Y Shirai
1Oral Medicine and Diagnosis, Dental Pharmacology, Pediatric Dentistry, Department of Oral Functional Science, Graduate School of Dental Medicine, Hokkaido University, Kita13 Nishi 7, Kika-ku, Hokkaido, Sapporo, 060-8586, Japan. take@den.hokudai.ac.jp
Biochemical and Biophysical Research Communications
|October 12, 2000
Summary
Osteoblasts regulate bone-resorbing osteoclast formation by sensing low calcium levels via the calcium-sensing receptor (CaSR). This mechanism influences osteoclast differentiation factor (ODF) expression, impacting bone remodeling.
Area of Science:
- Bone Biology
- Cell Signaling
- Mineral Metabolism
Background:
- Osteoclastogenesis, the formation of bone-resorbing cells, is crucial for bone remodeling.
- Low extracellular calcium environments are known to increase osteoclast numbers.
- The role of osteoblasts in mediating this calcium-dependent osteoclastogenesis requires further elucidation.
Purpose of the Study:
- To investigate the mechanism by which osteoblasts influence osteoclastogenesis in a low-calcium environment.
- To determine if osteoblasts utilize the calcium-sensing receptor (CaSR) to detect extracellular calcium levels.
- To assess the impact of CaSR activation on osteoclast differentiation factor (ODF) expression and osteoclast formation.
Main Methods:
- Coculture of MC3T3-E1 osteoblast-like cells with mouse bone marrow cells.
- Quantitative analysis of osteoclast numbers under varying calcium conditions.
- Measurement of osteoprotegerin ligand (OPGL)/osteoclast differentiation factor (ODF) mRNA expression.
- Stimulation of osteoblasts with CaSR agonists (gadolinium, neomycin).
Main Results:
- Low extracellular calcium significantly increased osteoclast numbers and OPGL/ODF mRNA expression in cocultures.
- The calcium-sensing receptor (CaSR) was detected on the surface of MC3T3-E1 osteoblasts.
- CaSR agonists reduced OPGL/ODF mRNA expression and osteoclast formation in coculture.
Conclusions:
- Osteoblasts likely recognize extracellular calcium levels through the CaSR.
- Activation of CaSR in osteoblasts leads to decreased expression of OPGL/ODF.
- This osteoblast-mediated CaSR signaling pathway plays a role in regulating osteoclastogenesis under low-calcium conditions.