Brain-Derived Neurotrophic Factor Enhances Periodontal Tissue Regeneration

Abstract

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.

Brain‐derived neurotrophic factor induces migration of endothelial cells through a TrkB–ERK–integrin αVβ3–FAK cascade

“…Our previous study has shown that many new blood vessels developed in BDNFinduced regenerated areas of periodontal tissue (Takeda et al, 2005). Since angiogenesis is a key phenomenon for tissue regeneration, the effect of BDNF on endothelial cell function should be clarified.…”

Brain-derived Neurotrophic Factor Stimulates Bone/Cementum-related Protein Gene Expression in Cementoblasts

“…Various types of non-neural cells and tissue express BDNF. At the cellular level, vascular endothelial cells, osteoblastic cells, periodontal ligament cells, and immune cells express BDNF (7)(8)(9)(10)(11). At the tissue level, BDNF is expressed in tooth germ, bone, cartilage, heart, spleen, placenta, prostate, and kidney (12)(13)(14)(15)(16).…”

“…Its formation is key to establishing functional periodontal tissue, which is structured with newly formed cementum, alveolar bone, and connective tissue fibers inserted into these hard tissues. We have focused on using BDNF to help regenerate periodontal tissue and found that the regulation of functions of periodontal ligament cells and endothelial cells by BDNF culminates in the promotion of periodontal tissue regeneration in vitro and in vivo (10). Furthermore, cementum forms in the early stages of the regeneration stimulated by BDNF (10).…”

“…We have focused on using BDNF to help regenerate periodontal tissue and found that the regulation of functions of periodontal ligament cells and endothelial cells by BDNF culminates in the promotion of periodontal tissue regeneration in vitro and in vivo (10). Furthermore, cementum forms in the early stages of the regeneration stimulated by BDNF (10). The mechanism whereby BDNF regulates cementoblast functions should be elucidated.…”

Periodontal Ligament Stem Cells

“…PDL cells have been reported to increase proliferation and the expressions of ALP and osteocalcin mRNA and osteopontin, BMP-2 and type I collagen synthesis through BDNF exposure (Tsuboi et al, 2001). Moreover, BDNF or BDNF/highmolecular-weight-hyaluronic acid reportedly increased the formation of new alveolar bone, cementum, Sharpey's fiber-like connective tissues and blood capillary in Class III furcation defects in a dog model (Takeda et al, 2005;Takeda et al, 2011).…”