The effect of the alendronate on OPG/RANKL system in differentiated primary human osteoblasts.
Alendronate is a well-established treatment for osteoporosis and suppresses bone resorption by a direct effect on osteoclasts and their precursors. The effect of alendronate on osteoclasts is produced, at least in part, by the receptor activator of nuclear factor kappaB ligand (RANKL) and the osteoprotegerin (OPG) synthesized by the osteoblasts. This study analyzes the effect of alendronate in cell viability, alkaline phosphatase (ALP) activity and RANKL and OPG expression in primary human osteoblasts (hOB). Alendronate at concentrations lower than 10⁻⁵ M did not have a toxic effect on hOB in vitro and did not modify the ALP activity at least for 72 h. Alendronate did not change OPG expression in basal, 10% fetal bovine serum (FBS), and vitamin D-treated cultures. Similar results were observed at the protein level. Unexpectedly, alendronate at 10⁻⁷ and 10⁻⁵ M concentrations increased the RANKL expression with the presence of vitamin D in differentiated hOB, and this induction of RANKL mRNA levels by alendronate was dose-dependent. However, this effect was not observed in basal and 10% FBS culture conditions. Thus, we conclude that alendronate does not affect the ALP activity and OPG gene expression in differentiated hOB, but may increase RANKL gene expression induced by vitamin D.
Metabolic Bone Diseases Unit, Department of Rheumatology, Hospital Clinic-IDIBAPS, University of Barcelona, Barcelona, Spain. enjuanes@clinic.ub.es
Anna
A
Enjuanes
Silvia
S
Ruiz-Gaspà
Pilar
P
Peris
Dolores
D
Ozalla
Luisa
L
Alvarez
Andrés
A
Combalia
M Jesús
MJ
Martínez de Osaba
Ana
A
Monegal
Albert
A
Pares
Nuria
N
Guañabens
D019386:Alendronate / Q000494:pharmacology*; D000469:Alkaline Phosphatase / Q000378:metabolism; D050071:Bone Density Conservation Agents / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects; D006801:Humans; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D053244:Osteoprotegerin / Q000235:genetics*; D053245:RANK Ligand / Q000235:genetics*; D012333:RNA, Messenger / Q000378:metabolism; D014807:Vitamin D / Q000494:pharmacology
D050071:Bone Density Conservation Agents; D053244:Osteoprotegerin; D053245:RANK Ligand; D012333:RNA, Messenger; C506030:TNFRSF11B protein, human; C505688:TNFSF11 protein, human; D014807:Vitamin D; D000469:Alkaline Phosphatase; D019386:Alendronate