Elevation of Extracellular Ca2+ Induces Store-Operated Calcium Entry via Calcium-Sensing Receptors: A Pathway Contributes to the Proliferation of Osteoblasts
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{"title"=>"Elevation of extracellular ca2+ induces store-operated calcium entry via calcium-sensing receptors: A pathway contributes to the proliferation of osteoblasts", "type"=>"journal", "authors"=>[{"first_name"=>"Fen", "last_name"=>"Hu", "scopus_author_id"=>"35573609000"}, {"first_name"=>"Leiting", "last_name"=>"Pan", "scopus_author_id"=>"25639839000"}, {"first_name"=>"Kai", "last_name"=>"Zhang", "scopus_author_id"=>"56373864200"}, {"first_name"=>"Fulin", "last_name"=>"Xing", "scopus_author_id"=>"56375035500"}, {"first_name"=>"Xinyu", "last_name"=>"Wang", "scopus_author_id"=>"55736814200"}, {"first_name"=>"Imshik", "last_name"=>"Lee", "scopus_author_id"=>"7404437956"}, {"first_name"=>"Xinzheng", "last_name"=>"Zhang", "scopus_author_id"=>"7410264685"}, {"first_name"=>"Jingjun", "last_name"=>"Xu", "scopus_author_id"=>"7407005822"}], "year"=>2014, "source"=>"PLoS ONE", "identifiers"=>{"sgr"=>"84907588671", "doi"=>"10.1371/journal.pone.0107217", "pui"=>"600067938", "pmid"=>"25254954", "scopus"=>"2-s2.0-84907588671", "issn"=>"19326203", "isbn"=>"1932-6203 (Electronic) 1932-6203 (Linking)"}, "id"=>"7dde33c2-4f10-3260-9b7c-4a912b9d235d", "abstract"=>"AIMS: The local concentration of extracellular Ca2+ ([Ca2+]o) in bone microenvironment is accumulated during bone remodeling. In the present study we investigated whether elevating [Ca2+]o induced store-operated calcium entry (SOCE) in primary rat calvarial osteoblasts and further examined the contribution of elevating [Ca2+]o to osteoblastic proliferation.\\n\\nMETHODS: Cytosolic Ca2+ concentration ([Ca2+]c) of primary cultured rat osteoblasts was detected by fluorescence imaging using calcium-sensitive probe fura-2/AM. Osteoblastic proliferation was estimated by cell counting, MTS assay and ATP assay. Agonists and antagonists of calcium-sensing receptors (CaSR) as well as inhibitors of phospholipase C (PLC), SOCE and voltage-gated calcium (Cav) channels were applied to study the mechanism in detail.\\n\\nRESULTS: Our data showed that elevating [Ca2+]o evoked a sustained increase of [Ca2+]c in a dose-dependent manner. This [Ca2+]c increase was blocked by TMB-8 (Ca2+ release inhibitor), 2-APB and BTP-2 (both SOCE blockers), respectively, whereas not affected by Cav channels blockers nifedipine and verapamil. Furthermore, NPS2143 (a CaSR antagonist) or U73122 (a PLC inhibitor) strongly reduced the [Ca2+]o-induced [Ca2+]c increase. The similar responses were observed when cells were stimulated with CaSR agonist spermine. These data indicated that elevating [Ca2+]o resulted in SOCE depending on the activation of CaSR and PLC in osteoblasts. In addition, high [Ca2+]o significantly promoted osteoblastic proliferation, which was notably reversed by BAPTA-AM (an intracellular calcium chelator), 2-APB, BTP-2, TMB-8, NPS2143 and U73122, respectively, but not affected by Cav channels antagonists.\\n\\nCONCLUSIONS: Elevating [Ca2+]o induced SOCE by triggering the activation of CaSR and PLC. This process was involved in osteoblastic proliferation induced by high level of extracellular Ca2+ concentration.", "link"=>"http://www.mendeley.com/research/elevation-extracellular-ca2-induces-storeoperated-calcium-entry-via-calciumsensing-receptors-pathway", "reader_count"=>23, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>4, "Researcher"=>3, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>2, "Student > Master"=>2, "Other"=>1, "Student > Bachelor"=>4, "Professor"=>1}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>1, "Student > Doctoral Student"=>4, "Researcher"=>3, "Student > Ph. D. Student"=>5, "Student > Postgraduate"=>2, "Student > Master"=>2, "Other"=>1, "Student > Bachelor"=>4, "Professor"=>1}, "reader_count_by_subject_area"=>{"Engineering"=>2, "Unspecified"=>3, "Biochemistry, Genetics and Molecular Biology"=>4, "Materials Science"=>1, "Agricultural and Biological Sciences"=>7, "Medicine and Dentistry"=>4, "Pharmacology, Toxicology and Pharmaceutical Science"=>2}, "reader_count_by_subdiscipline"=>{"Engineering"=>{"Engineering"=>2}, "Materials Science"=>{"Materials Science"=>1}, "Medicine and Dentistry"=>{"Medicine and Dentistry"=>4}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>7}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>4}, "Unspecified"=>{"Unspecified"=>3}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>2}}, "reader_count_by_country"=>{"United Kingdom"=>1, "Spain"=>1}, "group_count"=>0}

Scopus | Further Information

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1692077"], "description"=>"<p>(A) After calcium store depletion by a calcium pump blocker TG (1 µM) in Ca<sup>2+</sup>-free buffer, addition of 2 mM external Ca<sup>2+</sup> resulted in obvious calcium entry; then, further removal of external Ca<sup>2+</sup> caused [Ca<sup>2+</sup>]<sub>c</sub> decrease to baseline, suggesting the putative response for SOCE. (C, E) [Ca<sup>2+</sup>]<sub>c</sub> increase was caused by TG (1 µM) in Ca<sup>2+</sup>-free HBSS, followed by application of 25 µM 2-APB or 20 µM BTP-2 during the high [Ca<sup>2+</sup>]<sub>c</sub> plateau induced by re-addition of 2 mM external Ca<sup>2+</sup>, resulting in return to baseline [Ca<sup>2+</sup>]<sub>c</sub>. Statistic data of ratio of F340/F380 before and after the application of Ca<sup>2+</sup> free HBSS (B), 2-APB (D) and BTP-2 (F). * showed <i>P</i><0.05. (G) 1 µM TG was added after pretreatment with 25 µM 2-APB or 20 µM BTP-2 for 15 min, then, further addition of 2 mM external Ca<sup>2+</sup> had no effect on [Ca<sup>2+</sup>]<sub>c</sub> change. (H) Summary of the ratio of F340/F380 at 400 s from experiments shown in (G), * showed <i>P</i><0.05.</p>", "links"=>[], "tags"=>["rat calvarial osteoblasts", "extracellular", "CaSR agonist spermine", "assay", "Cav channels antagonists.ConclusionsElevating", "activation", "osteoblastic proliferation", "apb", "btp", "nps", "tmb", "atp", "soce", "calcium", "plc", "inhibitor", "concentration", "Cav channels blockers nifedipine", "mts", "data"], "article_id"=>1183213, "categories"=>["Biological Sciences"], "users"=>["Fen Hu", "Leiting Pan", "Kai Zhang", "Fulin Xing", "Xinyu Wang", "Imshik Lee", "Xinzheng Zhang", "Jingjun Xu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0107217.g001"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_TG_induced_SOCE_in_rat_calvarial_osteoblasts_/1183213", "title"=>"TG induced SOCE in rat calvarial osteoblasts.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-25 04:09:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/1692079"], "description"=>"<p>(A) Representative tracings of [Ca<sup>2+</sup>]<sub>c</sub> responses induced by [Ca<sup>2+</sup>]<sub>o</sub> at 0, 1, 2, 3, 5, 10 and 20 mM, respectively. (B) The statistic peak values of increase in F340/F380 ratio were plotted against [Ca<sup>2+</sup>]<sub>o</sub> (n = 15 for each case), * showed <i>P</i><0.05. The smooth curve represented the fitting to the equation of with an EC<sub>50</sub> value of 5.4±1.2 mM and Hill coefficient (n) of 2.2</p>", "links"=>[], "tags"=>["rat calvarial osteoblasts", "extracellular", "CaSR agonist spermine", "assay", "Cav channels antagonists.ConclusionsElevating", "activation", "osteoblastic proliferation", "apb", "btp", "nps", "tmb", "atp", "soce", "calcium", "plc", "inhibitor", "concentration", "Cav channels blockers nifedipine", "mts", "data"], "article_id"=>1183215, "categories"=>["Biological Sciences"], "users"=>["Fen Hu", "Leiting Pan", "Kai Zhang", "Fulin Xing", "Xinyu Wang", "Imshik Lee", "Xinzheng Zhang", "Jingjun Xu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0107217.g002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Elevated_Ca_2_o_resulted_in_Ca_2_c_increases_in_rat_calvarial_osteoblasts_/1183215", "title"=>"Elevated [Ca<sup>2+</sup>]<sub>o</sub> resulted in [Ca<sup>2+</sup>]<sub>c</sub> increases in rat calvarial osteoblasts.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-25 04:09:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/1692081"], "description"=>"<p>(A) Representative tracings of [Ca<sup>2+</sup>]<sub>c</sub> changes caused by elevating [Ca<sup>2+</sup>]<sub>o</sub> (10 mM) alone (control) and in the presence of nifedipine (10 µM) or verapamil (10 µM). Nifedipine or verapamil was added for 15 min before elevating [Ca<sup>2+</sup>]<sub>o</sub>. (B) Summary of the changes in F340/F380 at 250 s after the elevation of [Ca<sup>2+</sup>]<sub>o</sub> from experiments shown in (A). (C) Typical tracings of [Ca<sup>2+</sup>]<sub>c</sub> changes caused by elevating [K<sup>+</sup>]<sub>o</sub> (100 mM) alone (control) and in the presence of Ca<sup>2+</sup> free HBSS, nifedipine (10 µM) or verapamil (10 µM). Nifedipine or verapamil was added for 15 min before elevating [K<sup>+</sup>]<sub>o</sub>. (D) Summary of the peak values of increase in F340/F380 after the elevation of [K<sup>+</sup>]<sub>o</sub> from experiments shown in (C).</p>", "links"=>[], "tags"=>["rat calvarial osteoblasts", "extracellular", "CaSR agonist spermine", "assay", "Cav channels antagonists.ConclusionsElevating", "activation", "osteoblastic proliferation", "apb", "btp", "nps", "tmb", "atp", "soce", "calcium", "plc", "inhibitor", "concentration", "Cav channels blockers nifedipine", "mts", "data"], "article_id"=>1183217, "categories"=>["Biological Sciences"], "users"=>["Fen Hu", "Leiting Pan", "Kai Zhang", "Fulin Xing", "Xinyu Wang", "Imshik Lee", "Xinzheng Zhang", "Jingjun Xu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0107217.g003"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Nifedipine_or_verapamil_had_no_effect_on_Ca_2_o_induced_Ca_2_c_increase_in_rat_calvarial_osteoblasts_/1183217", "title"=>"Nifedipine or verapamil had no effect on [Ca<sup>2+</sup>]<sub>o</sub>-induced [Ca<sup>2+</sup>]<sub>c</sub> increase in rat calvarial osteoblasts.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-25 04:09:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/1692087"], "description"=>"<p>(A) Typical tracings of [Ca<sup>2+</sup>]<sub>c</sub> responses resulted from elevating [Ca<sup>2+</sup>]<sub>o</sub> (10 mM) in the absence (control) and in the presence of 2-APB (25 µM), BTP-2 (20 µM), or TMB-8 (50 µM). Such reagents were added for 15 min before the elevation of [Ca<sup>2+</sup>]<sub>o</sub>. (B) Summary of the changes in F340/F380 at 250 s after the elevation of [Ca<sup>2+</sup>]<sub>o</sub> from experiments shown in (A), * showed <i>P</i><0.05 comparing with control. (C, E, G) Representative tracings showing the effects of application of Ca<sup>2+</sup> free HBSS, 25 µM 2-APB or 20 µM BTP-2 on the high [Ca<sup>2+</sup>]<sub>c</sub> plateau induced by elevating [Ca<sup>2+</sup>]<sub>o</sub>. Statistic data of the ratio of F340/F380 before and after the application of Ca<sup>2+</sup> free HBSS (D), 2-APB (F) and BTP-2 (H), * showed <i>P</i><0.05.</p>", "links"=>[], "tags"=>["rat calvarial osteoblasts", "extracellular", "CaSR agonist spermine", "assay", "Cav channels antagonists.ConclusionsElevating", "activation", "osteoblastic proliferation", "apb", "btp", "nps", "tmb", "atp", "soce", "calcium", "plc", "inhibitor", "concentration", "Cav channels blockers nifedipine", "mts", "data"], "article_id"=>1183223, "categories"=>["Biological Sciences"], "users"=>["Fen Hu", "Leiting Pan", "Kai Zhang", "Fulin Xing", "Xinyu Wang", "Imshik Lee", "Xinzheng Zhang", "Jingjun Xu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0107217.g004"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Ca_2_o_induced_Ca_2_c_increase_was_blocked_by_2_APB_BTP_2_and_TMB_8_in_rat_calvarial_osteoblasts_respectively_/1183223", "title"=>"[Ca<sup>2+</sup>]<sub>o</sub>-induced [Ca<sup>2+</sup>]<sub>c</sub> increase was blocked by 2-APB, BTP-2 and TMB-8 in rat calvarial osteoblasts, respectively.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-25 04:09:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/1692094"], "description"=>"<p>(A) Representative tracings of [Ca<sup>2+</sup>]<sub>c</sub> changes induced by elevating [Ca<sup>2+</sup>]<sub>o</sub> (10 mM) alone (control) and in the presence of NPS2143 (10 µM), U73122 (5 µM) or U73343 (5 µM). Such reagents were added 15 min before application of the elevation of [Ca<sup>2+</sup>]<sub>o</sub>. (B) Summary of the changes in F340/F380 at 250 s after the elevation of [Ca<sup>2+</sup>]<sub>o</sub> from experiments shown in (A), * showed <i>P</i><0.05, compared with control in each group. (C) Typical tracings of [Ca<sup>2+</sup>]<sub>c</sub> responses induced by induced by 2 mM spermine in the presence (black) and absence (red) of external Ca<sup>2+</sup>. Cells were pretreated with 25 µM 2-APB (blue) or 20 µM BTP-2 (purple) for 15 min prior to spermine (2 mM) in Ca<sup>2+</sup>-containing HBSS. (D) Representative tracings of [Ca<sup>2+</sup>]<sub>c</sub> changes in response to 2 mM spermine in the presence of NPS2143 (10 µM), U73122 (5 µM) or U73343 (5 µM) in Ca<sup>2+</sup>-containging HBSS. Such reagents were added 15 min before adding spermine. (E) Summary of the changes in F340/F380 at 400 s after the stimulation with spermine in the presence Ca<sup>2+</sup> free HBSS, 2-APB, BTP-2, NPS2143, U73122 or U73343 from experiments shown in C and D, * showed <i>P</i><0.05 comparing with control (spermine alone) in each group.</p>", "links"=>[], "tags"=>["rat calvarial osteoblasts", "extracellular", "CaSR agonist spermine", "assay", "Cav channels antagonists.ConclusionsElevating", "activation", "osteoblastic proliferation", "apb", "btp", "nps", "tmb", "atp", "soce", "calcium", "plc", "inhibitor", "concentration", "Cav channels blockers nifedipine", "mts", "data"], "article_id"=>1183225, "categories"=>["Biological Sciences"], "users"=>["Fen Hu", "Leiting Pan", "Kai Zhang", "Fulin Xing", "Xinyu Wang", "Imshik Lee", "Xinzheng Zhang", "Jingjun Xu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0107217.g005"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Ca_2_o_induced_Ca_2_c_increase_was_dependent_on_the_activation_of_CaSR_PLC_signaling_in_rat_calvarial_osteoblasts_/1183225", "title"=>"[Ca<sup>2+</sup>]<sub>o</sub>-induced [Ca<sup>2+</sup>]<sub>c</sub> increase was dependent on the activation of CaSR/PLC signaling in rat calvarial osteoblasts.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-25 04:09:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/1692106"], "description"=>"<p>(A) Osteoblasts were cultured in medium containing different levels of [Ca<sup>2+</sup>]<sub>o</sub> or in a medium with 2 µM BAPTA-AM+10 mM [Ca<sup>2+</sup>]<sub>o</sub>. Typical cell morphological images were captured at 0 h, 24 h and 48 h and 72 h using a 10× objective. (B) Statistic data of cell numbers from experiments shown in (A). Each group of cells were grown in triplicate dishes and counted at different time points by measuring at least five regions (1 mm×1 mm grids). *<i>P</i><0.05, compared with control group (normal DMEM medium); # <i>P</i><0.05, compared with 10 mM [Ca<sup>2+</sup>]<sub>o</sub> group. (C) Summary of absorbance (A<sub>490</sub>) in each group. Absorbance (A<sub>490</sub>) assessed by MTS assay is proportional to the number of living cells. Osteoblasts were incubated for 72 h in culturing medium with different levels of [Ca<sup>2+</sup>]<sub>o</sub> or in a medium with 2 µM BAPTA-AM+10 mM [Ca<sup>2+</sup>]<sub>o</sub> (n = 7 for each case), * showed <i>P</i><0.05, compared with [Ca<sup>2+</sup>]<sub>o</sub>  = 1.8 mM group; # showed <i>P</i><0.05, compared with [Ca<sup>2+</sup>]<sub>o</sub>  = 10 mM group. (D) Statistic data of cell numbers in each group at different time points. Osteoblasts were cultured in medium containing 10 mM [Ca<sup>2+</sup>]<sub>o</sub> alone or together with 2-APB (25 µM), BTP-2 (20 µM), TMB-8 (50 µM), NPS2143 (10 µM), U73122 (5 µM), U73343 (5 µM), nifedipine (10 µM) and verapamil (10 µM), respectively. * showed <i>P</i><0.05 in comparison with [Ca<sup>2+</sup>]<sub>o</sub>  = 10 mM group. (E) Summary of absorbance (A<sub>490</sub>) measured after culturing for 72 h in [Ca<sup>2+</sup>]<sub>o</sub> = 10 mM medium alone or 2-APB (25 µM), BTP-2 (20 µM), TMB-8 (50 µM), NPS2143 (10 µM), U73122 (5 µM), U73343 (5 µM), nifedipine (10 µM) and verapamil (10 µM) (n = 7 for each case), respectively. * showed <i>P</i><0.05 compared with [Ca<sup>2+</sup>]<sub>o</sub> = 10 mM group.</p>", "links"=>[], "tags"=>["rat calvarial osteoblasts", "extracellular", "CaSR agonist spermine", "assay", "Cav channels antagonists.ConclusionsElevating", "activation", "osteoblastic proliferation", "apb", "btp", "nps", "tmb", "atp", "soce", "calcium", "plc", "inhibitor", "concentration", "Cav channels blockers nifedipine", "mts", "data"], "article_id"=>1183230, "categories"=>["Biological Sciences"], "users"=>["Fen Hu", "Leiting Pan", "Kai Zhang", "Fulin Xing", "Xinyu Wang", "Imshik Lee", "Xinzheng Zhang", "Jingjun Xu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0107217.g006"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Ca_2_o_induced_SOCE_was_involved_in_the_high_Ca_2_o_induced_proliferation_in_rat_calvarial_osteoblasts_/1183230", "title"=>"[Ca<sup>2+</sup>]<sub>o</sub>-induced SOCE was involved in the high [Ca<sup>2+</sup>]<sub>o</sub>-induced proliferation in rat calvarial osteoblasts.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-09-25 04:09:23"}
  • {"files"=>["https://ndownloader.figshare.com/files/1692110", "https://ndownloader.figshare.com/files/1692111"], "description"=>"<div><p>Aims</p><p>The local concentration of extracellular Ca<sup>2+</sup> ([Ca<sup>2+</sup>]<sub>o</sub>) in bone microenvironment is accumulated during bone remodeling. In the present study we investigated whether elevating [Ca<sup>2+</sup>]<sub>o</sub> induced store-operated calcium entry (SOCE) in primary rat calvarial osteoblasts and further examined the contribution of elevating [Ca<sup>2+</sup>]<sub>o</sub> to osteoblastic proliferation.</p><p>Methods</p><p>Cytosolic Ca<sup>2+</sup> concentration ([Ca<sup>2+</sup>]<sub>c</sub>) of primary cultured rat osteoblasts was detected by fluorescence imaging using calcium-sensitive probe fura-2/AM. Osteoblastic proliferation was estimated by cell counting, MTS assay and ATP assay. Agonists and antagonists of calcium-sensing receptors (CaSR) as well as inhibitors of phospholipase C (PLC), SOCE and voltage-gated calcium (Cav) channels were applied to study the mechanism in detail.</p><p>Results</p><p>Our data showed that elevating [Ca<sup>2+</sup>]<sub>o</sub> evoked a sustained increase of [Ca<sup>2+</sup>]<sub>c</sub> in a dose-dependent manner. This [Ca<sup>2+</sup>]<sub>c</sub> increase was blocked by TMB-8 (Ca<sup>2+</sup> release inhibitor), 2-APB and BTP-2 (both SOCE blockers), respectively, whereas not affected by Cav channels blockers nifedipine and verapamil. Furthermore, NPS2143 (a CaSR antagonist) or U73122 (a PLC inhibitor) strongly reduced the [Ca<sup>2+</sup>]<sub>o</sub>-induced [Ca<sup>2+</sup>]<sub>c</sub> increase. The similar responses were observed when cells were stimulated with CaSR agonist spermine. These data indicated that elevating [Ca<sup>2+</sup>]<sub>o</sub> resulted in SOCE depending on the activation of CaSR and PLC in osteoblasts. In addition, high [Ca<sup>2+</sup>]<sub>o</sub> significantly promoted osteoblastic proliferation, which was notably reversed by BAPTA-AM (an intracellular calcium chelator), 2-APB, BTP-2, TMB-8, NPS2143 and U73122, respectively, but not affected by Cav channels antagonists.</p><p>Conclusions</p><p>Elevating [Ca<sup>2+</sup>]<sub>o</sub> induced SOCE by triggering the activation of CaSR and PLC. This process was involved in osteoblastic proliferation induced by high level of extracellular Ca<sup>2+</sup> concentration.</p></div>", "links"=>[], "tags"=>["rat calvarial osteoblasts", "extracellular", "CaSR agonist spermine", "assay", "Cav channels antagonists.ConclusionsElevating", "activation", "osteoblastic proliferation", "apb", "btp", "nps", "tmb", "atp", "soce", "calcium", "plc", "inhibitor", "concentration", "Cav channels blockers nifedipine", "mts", "data"], "article_id"=>1183234, "categories"=>["Biological Sciences"], "users"=>["Fen Hu", "Leiting Pan", "Kai Zhang", "Fulin Xing", "Xinyu Wang", "Imshik Lee", "Xinzheng Zhang", "Jingjun Xu"], "doi"=>["https://dx.doi.org/10.1371/journal.pone.0107217.s001", "https://dx.doi.org/10.1371/journal.pone.0107217.s002"], "stats"=>{"downloads"=>0, "page_views"=>0, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Elevation_of_Extracellular_Ca_2_Induces_Store_Operated_Calcium_Entry_via_Calcium_Sensing_Receptors_A_Pathway_Contributes_to_the_Proliferation_of_Osteoblasts/1183234", "title"=>"Elevation of Extracellular Ca<sup>2+</sup> Induces Store-Operated Calcium Entry via Calcium-Sensing Receptors: A Pathway Contributes to the Proliferation of Osteoblasts", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2014-09-25 04:09:23"}

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