title: Locally Produced BDNF Promotes Sclerotic Change in Alveolar Bone after Nerve Injury.
abstract: Brain-derived neurotrophic factor (BDNF), which is released due to nerve injury, is known to promote the natural healing of injured nerves. It is often observed that damage of mandibular canal induces local sclerotic changes in alveolar bone. We reported that peripheral nerve injury promotes the local production of BDNF; therefore, it was possible to hypothesize that peripheral nerve injury affects sclerotic changes in the alveolar bone. This study aimed to evaluate the effect of BDNF on osteogenesis using in vitro osteoblast-lineage cell culture and an in vivo rat osteotomy model. MC3T3-E1 cells were cultured with BDNF and were examined for cell proliferative activity, chemotaxis and mRNA expression levels of osteoblast differentiation markers. For in vivo study, inferior alveolar nerve (IAN) injury experiments and mandibular cortical osteotomy were performed using a rat model. In the osteotomy model, exogenous BDNF was applied to bone surfaces after corticotomy of the mandible, and we morphologically analyzed the new bone formation. As a result, mRNA expression of osteoblast differentiation marker, osteocalcin, was significantly increased by BDNF, although cell proliferation and migration were not affected. In the in vivo study, osteopontin-positive new bone formation was significantly accelerated in the BDNF-grafted groups, and active bone remodeling, involving trkB-positive osteoblasts and osteocytes, continued after 28 days. In conclusion, BDNF stimulated the differentiation of MC3T3-E1 cells and it promoted new bone formation and maturation. These results suggested that local BDNF produced by peripheral nerve injury contributes to accelerating sclerotic changes in the alveolar bone.
authors.affiliation: Division of Anatomy and Cell Biology of the Hard Tissue, Niigata University Graduate School of Medical and Dental Sciences, Gakkocho-dori, Chuo-ku, Niigata, Japan.
authors.forename: Hiroko
authors.initials: H
authors.lastname: Ida-Yonemochi
authors.affiliation: Division of Dental Anesthesiology, Niigata University Graduate School of Medical and Dental Sciences, Gakkocho-dori, Chuo-ku, Niigata, Japan.
authors.forename: Yurie
authors.initials: Y
authors.lastname: Yamada
authors.affiliation: Division of Dental Anesthesiology, Niigata University Graduate School of Medical and Dental Sciences, Gakkocho-dori, Chuo-ku, Niigata, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Yoshikawa
authors.affiliation: Division of Dental Anesthesiology, Niigata University Graduate School of Medical and Dental Sciences, Gakkocho-dori, Chuo-ku, Niigata, Japan.
authors.forename: Kenji
authors.identifier: http://orcid.org/0000-0001-9126-9344
authors.initials: K
authors.lastname: Seo
mesh_terms: D000818:Animals; D016723:Bone Remodeling; D001842:Bone and Bones / Q000000981:diagnostic imaging / Q000294:innervation* / Q000473:pathology*; D019208:Brain-Derived Neurotrophic Factor / Q000378:metabolism* / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation; D002478:Cells, Cultured; D004195:Disease Models, Animal; D008340:Mandibular Nerve / Q000473:pathology; D051379:Mice; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010027:Osteotomy; D059348:Peripheral Nerve Injuries / Q000378:metabolism*; D051381:Rats; D012598:Sclerosis; D061221:Trigeminal Nerve Injuries / Q000378:metabolism
chemical_list: D019208:Brain-Derived Neurotrophic Factor