Osteoblast Ca(2+) permeability and voltage-sensitive Ca(2+) channel expression is temporally regulated by 1,25-dihydroxyvitamin D(3).
The cardiac subtype of the L-type voltage-sensitive Ca(2+) channel (VSCC) Cav1.2 (alpha(1C)) is the primary voltage-sensitive channel responsible for Ca(2+) influx into actively proliferating osteoblasts. This channel also serves as the major transducer of Ca(2+) signals in growth-phase osteoblasts in response to hormone treatment. In this study, we have demonstrated that 24-h treatment of MC3T3-E1 preosteoblasts with 1,25-dihydroxyvitamin D(3) [1,25(OH)(2)D(3)], a coupling factor for bone resorption, coordinately downregulates Cav1.2 (alpha(1C)) and uniquely upregulates T-type channel Cav3.2 (alpha(1H)). No other voltage-sensitive channel alpha-subunit of the 10 that were surveyed was upregulated by 1,25(OH)(2)D(3). The shift from predominantly L-type to T-type channel expression has been demonstrated to occur at both mRNA and protein levels detected using quantitative PCR and immunohistochemistry with antibodies specific for each channel type. Functional and pharmacological studies using specific inhibitors have revealed that treatment with 1,25(OH)(2)D(3) also alters the Ca(2+) permeability properties of the osteoblast membrane from a state of primarily L-current sensitivity to T-current sensitivity. We conclude that the L-type channel is likely to support proliferation of osteoblast cells, whereas T-type channels are more likely to be involved in supporting differentiated functions after 1,25(OH)(2)D(3)-mediated reversal of remodeling has occurred. This latter observation is consistent with the unique expression of the T-type VSCC Cav3.2 (alpha(1H)) in terminally differentiated osteocytes as we recently reported.
Bergh
Joel J
JJ
Department of Biological Sciences, University of Delaware, 326 Wolf Hall, Newark, DE 19716, USA.
Shao
Ying
Y
Puente
Erwin
E
Duncan
Randall L
RL
Farach-Carson
Mary C
MC
D016475:3T3 Cells; D000818:Animals; D002117:Calcitriol / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D015220:Calcium Channels / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D010539:Permeability; D021122:Protein Subunits; D012333:RNA, Messenger / Q000378:metabolism
D002120:Calcium Channel Agonists; D015220:Calcium Channels; D021122:Protein Subunits; D012333:RNA, Messenger; D002117:Calcitriol; D002118:Calcium