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.

Effects of new beta-type Ti-40Nb implant materials, brain-derived neurotrophic factor, acetylcholine and nicotine on human mesenchymal stem cells of osteoporotic and non osteoporotic donors

“…However, after 7 d BDNF did not increase the number of hMSCs. This corresponds with the result of Ida-Yonemochi et al (2017) who did not detect an increase in proliferation in MC3T3-E1 cells after 7 d [ 40 ]. In contrast, Cai et al (2010) showed that osteoblast proliferation increased after 6 d in a co-culture system of BDNF-producing Schwann cells and osteoblasts [ 41 ].…”

Effects of a Pasty Bone Cement Containing Brain-Derived Neurotrophic Factor-Functionalized Mesoporous Bioactive Glass Particles on Metaphyseal Healing in a New Murine Osteoporotic Fracture Model

“…Furthermore, it was shown that BDNF is involved in fracture healing since it was detected in fracture gap tissue but not during physiological bone remodeling [ 12 ]. Moreover, BDNF significantly increased new bone formation after applying BDNF to mandibular osteotomies of rats [ 13 ]. Therefore, BDNF appears as potential drug suitable to be incorporated in CPCs and to stimulate bone formation during fracture healing in osteoporosis.…”

Effects of BDNF and PEC Nanoparticles on Osteocytes

“…Liu et al verified the positive effect of 100 ng/mL BDNF on proliferation of human MSC [ 27 ]. In the murine osteoblast cell line MC3T3 proliferation was not enhanced by using 80 ng/mL of BDNF [ 19 ]. Thus, the appropriate concentration of BDNF for stimulation of proliferation is controversially discussed, and might be impaired by species and cell types.…”

“…The addition of BDNF to monocyte cultures during differentiation into osteoclasts did neither impair the osteoclastogenesis nor the activity of osteoclasts if they were harvested from healthy donors [ 16 , 17 ]. In non-tumorigenic animal models, e.g., in murine and rat fracture models, the application of BDNF revealed enhanced bone formation and fracture healing [ 18 , 19 ]. The positive effect of BDNF on fracture healing was also determined when BDNF was released from a bone substitute material [ 18 ].…”