Effects of a bisphosphonate on the expression of bone specific genes after autogenous free bone grafting in rats.
The purpose of this study was to evaluate the clinical availability of a bisphosphonate in autogenous free bone grafts. Bisphosphonate (0.01 mg/kg/day) was administered daily after an autogenous free bone graft on a rat calvarium. The effects of a bisphosphonate on the resorption of grafted bone and mRNA expression in bone specific genes, i.e. bone morphogenetic protein 2, bone morphogenetic protein 4, alkaline phosphatase, osteocalcin, osteoclast inhibitory factor and calcitonin receptor, were studied via a reverse transcription-polymerase chain reaction (RT-PCR), real time RT-PCR and tartrate-resistant alkaline phosphatase (TRAP) staining. In a clinical and histomorphological review, bone resorption decreased in the experimental group in contrast to the control group where active bone resorption was observed. Bisphosphonate altered not only the mRNA expression of the bone resorption associated genes but also the bone formation associated genes. The expression of the calcitonin receptor (CTR) mRNA was not detected and the osteoclast inhibitory factor (OCIF) was significantly up-regulated in the experimental group as opposed to the control group. The expressions of osteocalcin and alkaline phosphatase mRNAs were also higher in the experimental group. However, there was no significant difference in the mRNA expression of bone morphogenetic proteins between the two groups. The data suggest the possibility of a clinical application of bisphosphonates for decreasing resorption of grafted bone.
Myoung
H
H
Department of Oral and Maxillofacial Surgery, College of Dentistry and Craniofacial tissue Engineering Laboratory, Seoul National University, Korea.
Park
J Y
JY
Choung
P H
PH
D000135:Acid Phosphatase; D000469:Alkaline Phosphatase / Q000096:biosynthesis / Q000235:genetics; D000704:Analysis of Variance; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000096:biosynthesis / Q000235:genetics; D016723:Bone Remodeling / Q000187:drug effects* / Q000235:genetics*; D016025:Bone Transplantation / Q000502:physiology*; D001842:Bone and Bones / Q000378:metabolism; D004164:Diphosphonates / Q000494:pharmacology*; D005260:Female; D015870:Gene Expression / Q000187:drug effects; D006023:Glycoproteins / Q000096:biosynthesis / Q000235:genetics; D007527:Isoenzymes; D015675:Osteocalcin / Q000096:biosynthesis / Q000235:genetics; D053244:Osteoprotegerin; D000077268:Pamidronate; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018003:Receptors, Calcitonin / Q000096:biosynthesis / Q000235:genetics; D018160:Receptors, Cytoplasmic and Nuclear / Q000096:biosynthesis / Q000235:genetics; D018124:Receptors, Tumor Necrosis Factor; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012886:Skull; D018709:Statistics, Nonparametric; D000071681:Tartrate-Resistant Acid Phosphatase; D016212:Transforming Growth Factor beta; D015854:Up-Regulation
C525720:Bmp2 protein, rat; C525811:Bmp4 protein, rat; D055396:Bone Morphogenetic Protein 2; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D004164:Diphosphonates; D006023:Glycoproteins; D007527:Isoenzymes; D053244:Osteoprotegerin; D012333:RNA, Messenger; D018003:Receptors, Calcitonin; D018160:Receptors, Cytoplasmic and Nuclear; D018124:Receptors, Tumor Necrosis Factor; C506032:Tnfrsf11b protein, rat; D016212:Transforming Growth Factor beta; D015675:Osteocalcin; D000469:Alkaline Phosphatase; D000135:Acid Phosphatase; D000071681:Tartrate-Resistant Acid Phosphatase; D000077268:Pamidronate