Abstract
Near the bone remodeling compartments (BRC), extracellular calcium concentration (Ca2+o) is locally elevated and bone marrow stromal cells (BMSCs) close to the BRC can be exposed to high calcium concentration. The calcium-sensing receptor (CaSR) is known to play a key role in maintaining extracellular calcium homeostasis by sensing fluctuations in the levels of extracellular calcium (Ca2+o). When human BMSCs (hBMSCs) were exposed to various calcium concentrations (1.8, 3, 5, 10, 30 mM), moderate-high extracellular calcium concentrations (3–5 mM) stimulated proliferation, while a high calcium concentration (30 mM) inhibited the proliferation. Exposure to various calcium concentrations did not induce significant differences in the apoptotic cell fraction. Evaluation of multi-lineage differentiation potential showed no significant difference among various calcium concentration groups, except for the high calcium concentration (30 mM) treated group, which resulted in increased calcification after in vitro osteogenic differentiation. Treatment of NPS2143, a CaSR inhibitor, abolished the stimulatory effect on hBMSCs proliferation and migration indicating that CaSR is involved. These results suggest that the calcium concentration gradient near the BRC may play an important role in bone remodeling by acting as an osteoblast–osteoclast coupling mechanism through CaSR.
Highlights
Calcium plays an essential role in all living organisms, accounting for about 1–2%of adult human body weight
The results showed that an increase of Ca2+o stimulates human BMSCs (hBMSCs) proliferation and migration in a dosedependent manner in a Calcium-sensing receptor (CaSR) dependent way, based on the fact that NPS2143, a selective CaSR antagonist, abolishes the effects caused by a high Ca2+o concentration [20]
Increased Proliferation of Human Bone Marrow Stromal Cells in Moderate-High Calcium Concentration Is Mediated by Calcium-Sensing Receptor (CaSR)
Summary
Calcium plays an essential role in all living organisms, accounting for about 1–2%. of adult human body weight. CaSR is expressed in several tissues such as parathyroid, intestine, bone, and cartilage [5,6,7,8] and in a variety of cell types such as parathyroid cells, myeloma cells, fibroblasts, osteoblasts, and osteoclasts [9,10,11,12,13] to play a critical role in tissues maintaining Ca2+o homeostasis. Previous studies have reported that the Ca2+o gradient has several effects on the cells residing in BRCs including osteoblasts and osteoclasts. It is expected that a localized high calcium level produces the signal to inhibit bone resorption and stimulates bone formation by modulating the activity of hBMSCs toward bone formation. The results showed that an increase of Ca2+o stimulates hBMSC proliferation and migration in a dosedependent manner in a CaSR dependent way, based on the fact that NPS2143, a selective CaSR antagonist, abolishes the effects caused by a high Ca2+o concentration [20]
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