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

Near the bone remodeling compartments (BRC), extracellular calcium concentration (Ca<sup>2+</sup><sub>o</sub>) 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...

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Main Authors: Hyunji Cho, Jisoo Lee, Seoyoung Jang, Jungsun Lee, Tong In Oh, Youngsook Son, EunAh Lee
Format: Article
Language:English
Published: MDPI AG 2020-12-01
Series:International Journal of Molecular Sciences
Subjects:
Online Access:https://www.mdpi.com/1422-0067/22/1/325
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author Hyunji Cho
Jisoo Lee
Seoyoung Jang
Jungsun Lee
Tong In Oh
Youngsook Son
EunAh Lee
author_facet Hyunji Cho
Jisoo Lee
Seoyoung Jang
Jungsun Lee
Tong In Oh
Youngsook Son
EunAh Lee
author_sort Hyunji Cho
collection DOAJ
description Near the bone remodeling compartments (BRC), extracellular calcium concentration (Ca<sup>2+</sup><sub>o</sub>) 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 (Ca<sup>2+</sup><sub>o</sub>). 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.
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spelling doaj.art-cb9ab000bc224373bd226adbe85cae252023-11-21T03:11:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-12-0122132510.3390/ijms22010325CaSR-Mediated hBMSCs Activity Modulation: Additional Coupling Mechanism in Bone Remodeling CompartmentHyunji Cho0Jisoo Lee1Seoyoung Jang2Jungsun Lee3Tong In Oh4Youngsook Son5EunAh Lee6College of Life Science and Graduate School of Biotechnology, Kyung Hee University, Seochon-dong, Kiheung-go, Yongin-si, Geonggi-do 17104, KoreaDepartment of Medical Engineering, Graduate School, Kyung Hee University, Seoul 02447, KoreaDepartment of Medical Engineering, Graduate School, Kyung Hee University, Seoul 02447, KoreaR&D Institute, Biosolution Inc., Seoul 18111, KoreaDepartment of Biomedical Engineering, School of Medicine, Kyung Hee University, Seoul 02447, KoreaDepartment of Genetic Engineering, College of Life Science, Kyung Hee University, Seochon-dong, Kiheung-go, Yongin-si, Geonggi-do 17104, KoreaImpedance Imaging Research Center, Kyung Hee University, Seoul 02447, KoreaNear the bone remodeling compartments (BRC), extracellular calcium concentration (Ca<sup>2+</sup><sub>o</sub>) 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 (Ca<sup>2+</sup><sub>o</sub>). 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.https://www.mdpi.com/1422-0067/22/1/325bone remodelingcalcium-sensing receptorproliferationosteoblast-osteoclast coupling
spellingShingle Hyunji Cho
Jisoo Lee
Seoyoung Jang
Jungsun Lee
Tong In Oh
Youngsook Son
EunAh Lee
CaSR-Mediated hBMSCs Activity Modulation: Additional Coupling Mechanism in Bone Remodeling Compartment
International Journal of Molecular Sciences
bone remodeling
calcium-sensing receptor
proliferation
osteoblast-osteoclast coupling
title CaSR-Mediated hBMSCs Activity Modulation: Additional Coupling Mechanism in Bone Remodeling Compartment
title_full CaSR-Mediated hBMSCs Activity Modulation: Additional Coupling Mechanism in Bone Remodeling Compartment
title_fullStr CaSR-Mediated hBMSCs Activity Modulation: Additional Coupling Mechanism in Bone Remodeling Compartment
title_full_unstemmed CaSR-Mediated hBMSCs Activity Modulation: Additional Coupling Mechanism in Bone Remodeling Compartment
title_short CaSR-Mediated hBMSCs Activity Modulation: Additional Coupling Mechanism in Bone Remodeling Compartment
title_sort casr mediated hbmscs activity modulation additional coupling mechanism in bone remodeling compartment
topic bone remodeling
calcium-sensing receptor
proliferation
osteoblast-osteoclast coupling
url https://www.mdpi.com/1422-0067/22/1/325
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