Zoledronate, ibandronate and clodronate enhance osteoblast differentiation in a dose dependent manner--a quantitative in vitro gene expression analysis of Dlx5, Runx2, OCN, MSX1 and MSX2.
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Zoledronate, ibandronate and clodronate enhance osteoblast differentiation in a dose dependent manner--a quantitative in vitro gene expression analysis of Dlx5, Runx2, OCN, MSX1 and MSX2. / Koch, Felix Peter; Merkel, Christina; Al-Nawas, Bilal; Smeets, Ralf; Ziebart, Thomas; Walter, Christian; Wagner, Wilfried.
In: J CRANIO MAXILL SURG, Vol. 39, No. 8, 8, 2011, p. 562-569.Research output: SCORING: Contribution to journal › SCORING: Journal article › Research › peer-review
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TY - JOUR
T1 - Zoledronate, ibandronate and clodronate enhance osteoblast differentiation in a dose dependent manner--a quantitative in vitro gene expression analysis of Dlx5, Runx2, OCN, MSX1 and MSX2.
AU - Koch, Felix Peter
AU - Merkel, Christina
AU - Al-Nawas, Bilal
AU - Smeets, Ralf
AU - Ziebart, Thomas
AU - Walter, Christian
AU - Wagner, Wilfried
PY - 2011
Y1 - 2011
N2 - Bisphosphonates are widely used in the clinical treatment of bone diseases with increased bone resorption. In terms of side effects, they are known to be associated with osteonecrosis of the jaw (BONJ). There are two groups of bisphosphonates: the nitrogen-containing bisphosphonates, e.g. zoledronate and ibandronate, and the non-nitrogen-containing bisphosphonates, e.g. clodronate. Their impact on bone metabolism seems to differ. The objective of this study was to compare the osteogenic differentiation potency of these two pharmacologic groups. 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 periods of 1, 2, 5, 10 and 14 days. Clodronate was applied with concentrations of 5×10(-3), 5×10(-5) M and 5×10(-6) M. At each time point, the cells were dissolved, the mRNA extracted, and the gene expression level of the osteoblast specific differentiation markers of the homeobox transcription factors MSX1 and MSX2, the distal-less homeobox 5 (Dlx5), the Runt-related transcription factor 2 (Runx2/CBF1a) and osteocalcin (OCN) were quantified by Real-Time PCR. The gene expression was compared to an unstimulated osteoblast cell culture as control. The results showed a significant difference between the nitrogen-containing and the non-nitrogen-containing bisphosphonates. Zoledronate and ibandronate at concentrations of 5×10(-5) M enhanced the gene expression of all differentiation markers by several hundred folds compared to unstimulated control after 10 days, whereas clodronate had less influence on gene expression, even at higher concentrations of 5×10(-3) M. Lower concentrations of zoledronate and ibandronate, however, led to a decreased gene expression. These data confirm the results of other studies which have shown the osteogenic stimulus on osteoblasts in a dose dependent manner. The nitrogen-containing bisphosphonates appear to enhance bone density by stimulation of osteoblast differentiation. Non-nitrogen-containing bisphosphonates seem to have less influence on osteoblast differentiation.
AB - Bisphosphonates are widely used in the clinical treatment of bone diseases with increased bone resorption. In terms of side effects, they are known to be associated with osteonecrosis of the jaw (BONJ). There are two groups of bisphosphonates: the nitrogen-containing bisphosphonates, e.g. zoledronate and ibandronate, and the non-nitrogen-containing bisphosphonates, e.g. clodronate. Their impact on bone metabolism seems to differ. The objective of this study was to compare the osteogenic differentiation potency of these two pharmacologic groups. 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 periods of 1, 2, 5, 10 and 14 days. Clodronate was applied with concentrations of 5×10(-3), 5×10(-5) M and 5×10(-6) M. At each time point, the cells were dissolved, the mRNA extracted, and the gene expression level of the osteoblast specific differentiation markers of the homeobox transcription factors MSX1 and MSX2, the distal-less homeobox 5 (Dlx5), the Runt-related transcription factor 2 (Runx2/CBF1a) and osteocalcin (OCN) were quantified by Real-Time PCR. The gene expression was compared to an unstimulated osteoblast cell culture as control. The results showed a significant difference between the nitrogen-containing and the non-nitrogen-containing bisphosphonates. Zoledronate and ibandronate at concentrations of 5×10(-5) M enhanced the gene expression of all differentiation markers by several hundred folds compared to unstimulated control after 10 days, whereas clodronate had less influence on gene expression, even at higher concentrations of 5×10(-3) M. Lower concentrations of zoledronate and ibandronate, however, led to a decreased gene expression. These data confirm the results of other studies which have shown the osteogenic stimulus on osteoblasts in a dose dependent manner. The nitrogen-containing bisphosphonates appear to enhance bone density by stimulation of osteoblast differentiation. Non-nitrogen-containing bisphosphonates seem to have less influence on osteoblast differentiation.
KW - Humans
KW - Time Factors
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Dose-Response Relationship, Drug
KW - Cell Culture Techniques
KW - Cell Differentiation/drug effects
KW - Gene Expression Regulation/drug effects
KW - Osteoblasts/drug effects
KW - Biological Markers/analysis
KW - Bone Density Conservation Agents/administration & dosage/pharmacology
KW - Bone Remodeling/drug effects
KW - Clodronic Acid/pharmacology
KW - Core Binding Factor Alpha 1 Subunit/analysis
KW - Diphosphonates/administration & dosage/pharmacology
KW - Homeodomain Proteins/analysis
KW - Imidazoles/pharmacology
KW - MSX1 Transcription Factor/analysis
KW - Osteocalcin/analysis
KW - Transcription Factors/analysis
KW - Humans
KW - Time Factors
KW - Reverse Transcriptase Polymerase Chain Reaction
KW - Dose-Response Relationship, Drug
KW - Cell Culture Techniques
KW - Cell Differentiation/drug effects
KW - Gene Expression Regulation/drug effects
KW - Osteoblasts/drug effects
KW - Biological Markers/analysis
KW - Bone Density Conservation Agents/administration & dosage/pharmacology
KW - Bone Remodeling/drug effects
KW - Clodronic Acid/pharmacology
KW - Core Binding Factor Alpha 1 Subunit/analysis
KW - Diphosphonates/administration & dosage/pharmacology
KW - Homeodomain Proteins/analysis
KW - Imidazoles/pharmacology
KW - MSX1 Transcription Factor/analysis
KW - Osteocalcin/analysis
KW - Transcription Factors/analysis
M3 - SCORING: Journal article
VL - 39
SP - 562
EP - 569
JO - J CRANIO MAXILL SURG
JF - J CRANIO MAXILL SURG
SN - 1010-5182
IS - 8
M1 - 8
ER -
