Brain-derived neurotrophic factor enhances periodontal tissue regeneration.
To address whether brain-derived neurotrophic factor (BDNF) could be involved in periodontal tissue regeneration, we examined the effects of BDNF on proliferation and the expression of bone (cementum)- related proteins (osteopontin, bone morphogenetic protein [BMP]-2, type I collagen, alkaline phosphatase [ALPase], and osteocalcin) in cultures of human periodontal ligament (HPL) cells, which are thought to be prerequisite for periodontal tissue regeneration, and on proliferation and angiogenesis in human endothelial cells. Furthermore, we examined the effect of BDNF on the regeneration of periodontal tissues in experimentally induced periodontal defects in dogs. BDNF elevated the expression of ALPase and osteocalcin mRNAs and increased the synthesis of osteopontin, BMP-2, and type I collagen DNA in HPL cells. BDNF stimulated mRNA expression of vascular endothelial growth factor-B and tenascin-X, and proliferation and angiogenesis in human endothelial cells. In vivo studies showed that BDNF stimulated the formation of new alveolar bone cementum and connective new fibers, which were inserted into the newly formed cementum and bone. BDNF also stimulated blood capillary formation. These findings suggest that the regulation of functioning of periodontal ligament cells and endothelial cells by BDNF results in the promotion of periodontal tissue regeneration.
Takeda
Katsuhiro
K
Department of Periodontal Medicine, Division of Frontier Medical Science, Hiroshima University Graduate School of Biomedical Sciences, Hiroshima, Japan.
Shiba
Hideki
H
Mizuno
Noriyoshi
N
Hasegawa
Naohiko
N
Mouri
Yoshihiro
Y
Hirachi
Akio
A
Yoshino
Hiroshi
H
Kawaguchi
Hiroyuki
H
Kurihara
Hidemi
H
D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins / Q000032:analysis / Q000378:metabolism; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology*; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D018920:Coculture Techniques; D024042:Collagen Type I / Q000378:metabolism; D004247:DNA / Q000096:biosynthesis; D003739:Dental Cementum / Q000166:cytology / Q000187:drug effects / Q000201:enzymology / Q000378:metabolism; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D004730:Endothelium, Vascular / Q000166:cytology / Q000502:physiology; D005260:Female; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism; D019084:Fluorescent Antibody Technique, Indirect; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D007150:Immunohistochemistry; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009924:Organ Culture Techniques; D015675:Osteocalcin / Q000378:metabolism; D053495:Osteopontin; D010513:Periodontal Ligament / Q000166:cytology* / Q000187:drug effects / Q000502:physiology*; D011347:Procollagen / Q000032:analysis / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012038:Regeneration / Q000187:drug effects*; D012795:Sialoglycoproteins / Q000032:analysis / Q000378:metabolism; D012867:Skin / Q000166:cytology; D019063:Tenascin / Q000378:metabolism; D013997:Time Factors; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000378:metabolism; D014471:Umbilical Veins / Q000166:cytology
C525718:BMP2 protein, human; D055396:Bone Morphogenetic Protein 2; D019485:Bone Morphogenetic Proteins; D019208:Brain-Derived Neurotrophic Factor; D024042:Collagen Type I; D011347:Procollagen; D012333:RNA, Messenger; C506895:SPP1 protein, human; D012795:Sialoglycoproteins; D019063:Tenascin; D016212:Transforming Growth Factor beta; C081865:tenascin X; D015675:Osteocalcin; D053495:Osteopontin; D004247:DNA; D000469:Alkaline Phosphatase