Statin-induced bone morphogenetic protein (BMP) 2 expression during bone regeneration: an immunohistochemical study
Received 25 March 2008; received in revised form 30 May 2008; accepted 25 June 2008. published online 29 August 2008.
Objectives
The purpose of this study was to investigate bone morphogenetic protein (BMP) 2 expression after implantation of a statin and recombinant human BMP-2 (rhBMP-2) and to compare the bone regeneration capability of these substances in the rabbit nasal bone using immunohistologic methods.
Study design
Twelve adult male Japanese white rabbits (n = 12; age 12-16 weeks, weight 2.5-3.0 kg) were divided into 3 experimental groups and 1 control group. A total of 48 bone defects, 4 per rabbit, were created in the nasal bone while preserving the nasal membrane. In the experimental groups, 1 group was implanted with 10 mg of a statin dissolved in 0.2 mL water with an atelocollagen sponge (ACS); the second group was implanted with 5 μg rhBMP-2 with an ACS; and in the third group only the ACS was implanted. No material was implanted in the control group. Animals were killed at 1, 2, and 4 weeks after surgery. The parts that had been operated on were removed and prepared for histologic assessment. The expression of BMP-2 was evaluated using immunohistochemistry, and double-immunostaining for BMP-2 and Ki-67 was observed by fluorescent microscopy.
Results
No significant differences were observed between the statin/ACS group and rhBMP-2/ACS group at 1, 2, and 4 weeks after surgery. The number of cells which stained positively for BMP-2 increased significantly in both of the implanted groups compared with the control group (P < .0001). The positive fluorescent double-immunostaining for BMP-2 and Ki-67 was similar in both implanted groups.
Conclusion
This study suggests that statin/ACS implants show BMP-2 expression and osteoinductive activity that is similar to those of rhBMP-2/ACS implants.
aClinical Fellow, Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan
bAssistant Professor, Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan
cAssociate Professor, Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan
dProfessor, Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan
eResearch Fellow, Department of Histology and Embryology, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan
fProfessor, Department of Histology and Embryology, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan
Reprint requests: Koichiro Ueki, DDS, PhD, Department of Oral and Maxillofacial Surgery, Graduate School of Medicine, Kanazawa University, 13-1 Takaramachi, Kanazawa 920-8641, Japan
Mevalotin (pravastatin sodium) supplied by Sankyo Seiyaku; rhBMP-2 supplied by Yamanouchi (Astellas) Pharmaceutical Co.
ABSTRACT