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Alendronate Interacts With the Inhibitory Effect of 1,25(OH) 2 D 3 on Parathyroid Hormone‐Related Protein Expression In Human Osteoblastic Cells
Author(s) -
GómezGarcía L,
Esbrit P,
Carreño L,
Sabando P,
GarcíaFlores M,
Martinez ME
Publication year - 2003
Publication title -
journal of bone and mineral research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.882
H-Index - 241
eISSN - 1523-4681
pISSN - 0884-0431
DOI - 10.1359/jbmr.2003.18.1.78
Subject(s) - osteocalcin , medicine , endocrinology , parathyroid hormone , bone resorption , bisphosphonate , chemistry , immunoradiometric assay , secretion , messenger rna , calcitriol receptor , resorption , receptor , parathyroid hormone related protein , osteopontin , vitamin d and neurology , osteoblast , calcium , alkaline phosphatase , in vitro , radioimmunoassay , osteoporosis , biochemistry , gene , enzyme
The bisphosphonate alendronate is a potent inhibitor of bone resorption by its direct action on osteoclasts. In addition, there is some data suggesting that alendronate could also inhibit bone resorption indirectly by interacting with osteoblasts. Parathyroid hormone‐related protein (PTHrP) produced by osteoblasts and 1,25‐dihydroxyvitamin D 3 [1,25(OH) 2 D 3 ] are regulators of bone remodeling, which have interrelated actions in these cells. In this study, we assessed whether alendronate can affect PTHrP expression in the presence or absence of 1,25(OH) 2 D 3 in human primary osteoblastic (hOB) cells from trabecular bone. Cell total RNA was isolated, and semiquantitative reverse transcription‐polymerase chain reaction (RT‐PCR) was carried out using human PTHrP‐specific primers. PTHrP in the hOB cell‐conditioned medium was analyzed by a specific immunoradiometric assay. We found that PTHrP mRNA and secreted PTHrP were maximally inhibited by 10 −8 ‐10 −6 M of 1,25(OH) 2 D 3 treatment within 8–72 h in hOB cells. Alendronate (10 −14 ‐10 −8 M) modified neither PTHrP mRNA nor PTHrP secretion, although it consistently abrogated the decrease in PTHrP production induced by 1,25(OH) 2 D 3 in these cells. On the other hand, alendronate within the same dose range did not affect either the vitamin D receptor (VDR) mRNA or osteocalcin secretion, with or without 1,25(OH) 2 D 3 , in hOB cells. The inhibitory effect of alendronate on the 1,25(OH) 2 D 3 ‐induced decrease in PTHrP in these cells was mimicked by the calcium ionophore A23187 (5 × 10 −6 M), while it was eliminated by 5 × 10 −5 M of nifedipine. Furthermore, although alendronate alone failed to affect [Ca 2+ ] i in these cells, it stimulated [Ca 2+ ] i after pretreatment of hOB cells with 10 −8 M of 1,25(OH) 2 D 3 , an effect that was abolished by 5 × 10 −5 M of nifedipine. These results show that alendronate disrupts the modulatory effect of 1,25(OH) 2 D 3 on PTHrP production in hOB cells. Our findings indicate that an increase in calcium influx appears to be involved in the mechanism mediating this effect of alendronate.