Influence of bisphosphonates on the osteoblast RANKL and OPG gene expression in vitro.
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Influence of bisphosphonates on the osteoblast RANKL and OPG gene expression in vitro. / Koch, Felix Peter; Merkel, Christina; Ziebart, Thomas; Smeets, Ralf; Walter, Christian; Al-Nawas, Bilal.
in: CLIN ORAL INVEST, Jahrgang 16, Nr. 1, 1, 2012, S. 79-86.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Influence of bisphosphonates on the osteoblast RANKL and OPG gene expression in vitro.
AU - Koch, Felix Peter
AU - Merkel, Christina
AU - Ziebart, Thomas
AU - Smeets, Ralf
AU - Walter, Christian
AU - Al-Nawas, Bilal
PY - 2012
Y1 - 2012
N2 - Bisphosphonates are widely used in the clinical treatment of bone diseases with increased bone resorption. In terms of side effects, they are widely known to be associated with osteonecrosis of the jaw (BONJ). The objective of this study was to evaluate the effect of bisphosphonates on the gene expression of receptor activator of NF-?B ligand (RANKL) and osteoprotegerin (OPG) in vitro. Nitrogen-containing and non-nitrogen containing bisphosphonates have been compared. Human osteoblasts were stimulated with zoledronate and ibandronate at concentrations of 5 × 10(-5) M, 5 × 10(-6) M, and 5 × 10(-7) M over the experimental period of 14 days. Furthermore, the hOB cell lines were stimulated by clodronate at concentrations of 5 × 10(-3) M, 5 × 10(-5) M, and 5 × 10(-6) M. At each point in time, the gene expression levels of RANKL and OPG were quantified by real-time RT-PCR. The results showed a moderate enhancement of OPG gene expression whereas RANKL gene expression was strongly increased by nitrogen-containing bisphosphonates reaching a maximum after 14 days at high concentrations of 5 × 10(-5) M. Lower concentrations did not enhance the RANKL and OPG expression considerably. The non-nitrogen-containing bisphosphonate clodronate, however, effected OPG and RANKL gene expression much less, even at higher concentrations of 5 × 10(-3) M. The above-mentioned data suggest an enhanced RANKL/OPG gene expression after stimulation by bisphosphonates. Interestingly, clodronate might have little influence on osteoblast/osteoclast interaction with respect to OPG and RANKL gene expression.
AB - Bisphosphonates are widely used in the clinical treatment of bone diseases with increased bone resorption. In terms of side effects, they are widely known to be associated with osteonecrosis of the jaw (BONJ). The objective of this study was to evaluate the effect of bisphosphonates on the gene expression of receptor activator of NF-?B ligand (RANKL) and osteoprotegerin (OPG) in vitro. Nitrogen-containing and non-nitrogen containing bisphosphonates have been compared. Human osteoblasts were stimulated with zoledronate and ibandronate at concentrations of 5 × 10(-5) M, 5 × 10(-6) M, and 5 × 10(-7) M over the experimental period of 14 days. Furthermore, the hOB cell lines were stimulated by clodronate at concentrations of 5 × 10(-3) M, 5 × 10(-5) M, and 5 × 10(-6) M. At each point in time, the gene expression levels of RANKL and OPG were quantified by real-time RT-PCR. The results showed a moderate enhancement of OPG gene expression whereas RANKL gene expression was strongly increased by nitrogen-containing bisphosphonates reaching a maximum after 14 days at high concentrations of 5 × 10(-5) M. Lower concentrations did not enhance the RANKL and OPG expression considerably. The non-nitrogen-containing bisphosphonate clodronate, however, effected OPG and RANKL gene expression much less, even at higher concentrations of 5 × 10(-3) M. The above-mentioned data suggest an enhanced RANKL/OPG gene expression after stimulation by bisphosphonates. Interestingly, clodronate might have little influence on osteoblast/osteoclast interaction with respect to OPG and RANKL gene expression.
KW - Humans
KW - Time Factors
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Cell Line
KW - Dose-Response Relationship, Drug
KW - Cell Culture Techniques
KW - Gene Expression Regulation/drug effects
KW - Osteoblasts/drug effects
KW - Bone Density Conservation Agents/administration & dosage/pharmacology
KW - Diphosphonates/administration & dosage/pharmacology
KW - Real-Time Polymerase Chain Reaction
KW - Clodronic Acid/administration & dosage/pharmacology
KW - Imidazoles/administration & dosage/pharmacology
KW - Osteoprotegerin/drug effects/genetics
KW - RANK Ligand/drug effects/genetics
KW - Humans
KW - Time Factors
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Cell Line
KW - Dose-Response Relationship, Drug
KW - Cell Culture Techniques
KW - Gene Expression Regulation/drug effects
KW - Osteoblasts/drug effects
KW - Bone Density Conservation Agents/administration & dosage/pharmacology
KW - Diphosphonates/administration & dosage/pharmacology
KW - Real-Time Polymerase Chain Reaction
KW - Clodronic Acid/administration & dosage/pharmacology
KW - Imidazoles/administration & dosage/pharmacology
KW - Osteoprotegerin/drug effects/genetics
KW - RANK Ligand/drug effects/genetics
M3 - SCORING: Journal article
VL - 16
SP - 79
EP - 86
JO - CLIN ORAL INVEST
JF - CLIN ORAL INVEST
SN - 1432-6981
IS - 1
M1 - 1
ER -
