CaSR-Mediated hBMSCs Activity Modulation: Additional Coupling Mechanism in Bone Remodeling Compartment.

Area of Science:

• Cell Biology
• Biochemistry
• Bone Physiology

Background:

• Bone remodeling compartments (BRC) feature localized high extracellular calcium (Ca²⁺_o).
• Bone marrow stromal cells (BMSCs) near BRC are exposed to these calcium gradients.
• The calcium-sensing receptor (CaSR) is crucial for calcium homeostasis.

Purpose of the Study:

• To investigate the effect of varying extracellular calcium concentrations on human BMSCs (hBMSCs).
• To determine the role of CaSR in mediating these cellular responses.
• To elucidate the potential role of calcium gradients in bone remodeling.

Main Methods:

• hBMSCs were exposed to diverse calcium concentrations (1.8–30 mM).
• Cell proliferation, apoptosis, and multi-lineage differentiation were assessed.
• CaSR inhibitor (NPS2143) was used to evaluate receptor involvement.

Main Results:

• Moderate-high calcium (3–5 mM) stimulated hBMSC proliferation; high calcium (30 mM) inhibited it.
• Apoptosis was not significantly affected, but high calcium increased in vitro osteogenic calcification.
• CaSR inhibition abolished the stimulatory effect on proliferation and migration.

Conclusions:

• Extracellular calcium concentration gradients near BRC influence hBMSC behavior.
• CaSR mediates the proliferative and migratory responses of hBMSCs to calcium.
• Calcium gradients may act as an osteoblast-osteoclast coupling mechanism in bone remodeling via CaSR.