Peptide-induced de novo bone formation after tooth extraction prevents alveolar bone loss in a murine tooth extraction model.
Tooth extraction causes bone resorption of the alveolar bone volume. Although recombinant human bone morphogenetic protein 2 (rhBMP-2) markedly promotes de novo bone formation after tooth extraction, the application of high-dose rhBMP-2 may induce side effects, such as swelling, seroma, and an increased cancer risk. Therefore, reduction of the necessary dose of rhBMP-2 which can still obtain sufficient bone mass is necessary by developing a new osteogenic reagent. Recently, we showed that the systemic administration of OP3-4 peptide, which was originally designed as a bone resorption inhibitor, had osteogenic ability both in vitro and in vivo. This study evaluated the ability of the local application of OP3-4 peptide to promote bone formation in a murine tooth extraction model with a very low-dose of BMP. The mandibular incisor was extracted from 10-week-old C57BL6/J male mice and a gelatin hydrogel containing rhBMP-2 with or without OP3-4 peptide (BMP/OP3-4) was applied to the socket of the incisor. Bone formation inside the socket was examined radiologically and histologically at 21 days after the extraction. The BMP/OP3-4-group showed significant bone formation inside the mandibular extraction socket compared to the gelatin-hydrogel-carrier-control group or rhBMP-2-applied group. The BMP/OP3-4-applied mice showed a lower reduction of alveolar bone and fewer osteoclast numbers, suggesting that the newly formed bone inside the socket may prevent resorption of the cortical bone around the extraction socket. Our data revealed that OP3-4 peptide promotes BMP-mediated bone formation inside the extraction socket of mandibular bone, resulting in preservation from the loss of alveolar bone.
Removable Partial Prosthodontics, Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan; Bio-Matrix (Pharmacology), Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
Yuki
Y
Arai
Bio-Matrix (Pharmacology), Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan. Electronic address: kazu.hpha@tmd.ac.jp.
Kazuhiro
K
Aoki
Orthodontic Science, Division of Oral Health Sciences, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8549, Japan.
Yasuhiro
Y
Shimizu
Department of Biomaterials, Field of Tissue Engineering, Institute for Frontier Medical Sciences, Kyoto University, Sakyo-ku, Kyoto 6068507, Japan.
Yasuhiko
Y
Tabata
Orthodontic Science, Division of Oral Health Sciences, Graduate School, Tokyo Medical and Dental University, Tokyo 113-8549, Japan.
Takashi
T
Ono
Department of Biomedical Sciences, Research Division of Immunology, Cedars-Sinai Medical Center, Los Angeles, CA 9004, USA.
Ramachandran
R
Murali
Bio-Matrix (Pharmacology), Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
Setsuko
S
Mise-Omata
Removable Partial Prosthodontics, Oral Health Sciences, Graduate School of Medical and Dental Sciences, Tokyo Medical and Dental University, 1-5-45 Yushima, Bunkyo-ku, Tokyo 113-8549, Japan.
Noriyuki
N
Wakabayashi
D016301:Alveolar Bone Loss / Q000209:etiology* / Q000503:physiopathology / Q000517:prevention & control*; D000818:Animals; D055396:Bone Morphogenetic Protein 2 / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D006801:Humans; D007180:Incisor / Q000601:surgery; D008297:Male; D051379:Mice; D009842:Oligopeptides / Q000494:pharmacology*; D010012:Osteogenesis / Q000187:drug effects*; D014081:Tooth Extraction / Q000009:adverse effects*; D020390:Tooth Socket / Q000187:drug effects / Q000502:physiology
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; C484520:OP3-4 peptide; D009842:Oligopeptides
Alveolar ridge preservation; BMP-2; Bone formation; Osteoprotegerin; Peptide therapeutics; Tooth extraction