PMID- 29490590 OWN - NLM STAT- MEDLINE DCOM- 20190207 LR - 20190215 IS - 1937-335X (Electronic) IS - 1937-3341 (Linking) VI - 24 IP - 15-16 DP - 2018 Aug TI - Effect of Brain-Derived Neurotrophic Factor on the Neurogenesis and Osteogenesis in Bone Engineering. PG - 1283-1292 LID - 10.1089/ten.TEA.2017.0462 [doi] AB - During bone growth, the lack of a neuralized vascular network in the regenerating area can affect subsequent bone quality. This study aimed to investigate if brain-derived neurotrophic factor (BDNF) could promote neurogenesis and osteogenesis in human bone mesenchymal stem cells (hBMSCs) to improve bone formation during tissue engineering. Initially, a safe and effective BDNF concentration that facilitated hBMSC proliferation in vitro was determined. Subsequently, examination of mineralized nodule formation and evaluation of alkaline phosphatase (ALP) activity and ALP gene expression revealed that the most effective concentration of BDNF to elicit a response in hBMSCs was 100 ng/mL. In addition, we found out that by binding with TrkB receptor, the downstream Erk1/2 was phosphorylated, which promoted the expression of transcription factors, such as Runx2 and Osterix that are associated with osteoblast differentiation. We also found that by day 7 post-treatment, the neurogenic biomarkers, p75 and s100, were highly expressed in 100 ng/mL BDNF-treated hBMSCs. Finally, the effects of BDNF on osteogenesis and neurogenesis in newly formed tissues were assessed using animal models with a beta-tricalcium phosphate scaffold. This revealed that treatment with 100 ng/mL BDNF promoted the osteogenesis and neurogenesis of hBMSCs in vivo by increasing expression of the osteogenic marker osteocalcin and various neurogenic biomarkers, including microtubule-associated protein 2, glial fibrillary acidic protein, neural/glial antigen 2, and beta-tubulin III. This study has demonstrated that BDNF promotes hBMSC osteogenesis and neurogenesis in vitro and in vivo, and that BDNF may indirectly promote osteogenesis through increased neurogenesis. This further suggests that encouraging neutralization during bone engineering will lead to effective repairing of bone defects. The study may also provide insight into related fields, such as osseoperception and stress feedback regulation after dental implantation. FAU - Liu, Qing AU - Liu Q AD - 1 Department of Prosthodontics, Peking University School and Hospital of Stomatology , Beijing, P.R. China . AD - 2 Department of Stomatology, Peking University International Hospital , Beijing, P.R. China . FAU - Lei, Lei AU - Lei L AD - 1 Department of Prosthodontics, Peking University School and Hospital of Stomatology , Beijing, P.R. China . FAU - Yu, Tao AU - Yu T AD - 1 Department of Prosthodontics, Peking University School and Hospital of Stomatology , Beijing, P.R. China . AD - 3 First Clinical Division, Peking University School and Hospital of Stomatology , Beijing, P.R. China . FAU - Jiang, Ting AU - Jiang T AD - 1 Department of Prosthodontics, Peking University School and Hospital of Stomatology , Beijing, P.R. China . FAU - Kang, Yunqing AU - Kang Y AD - 4 Department of Ocean and Mechanical Engineering, College of Engineering and Computer Science, College of Medicine, Florida Atlantic University , Boca Raton, Florida. AD - 5 Department of Biomedical Science, College of Medicine, Florida Atlantic University , Boca Raton, Florida. LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20180410 PL - United States TA - Tissue Eng Part A JT - Tissue engineering. Part A JID - 101466659 RN - 0 (Antigens, Differentiation) RN - 0 (Brain-Derived Neurotrophic Factor) SB - IM MH - Antigens, Differentiation/biosynthesis MH - Bone and Bones/cytology/*metabolism MH - Brain-Derived Neurotrophic Factor/*pharmacology MH - Cells, Cultured MH - Humans MH - Mesenchymal Stem Cells/cytology/*metabolism MH - Neurogenesis/*drug effects MH - Osteogenesis/*drug effects MH - *Tissue Engineering OTO - NOTNLM OT - biomarkers OT - mesenchymal stem cells OT - neurogenesis OT - osteogenesis OT - tissue regeneration EDAT- 2018/03/02 06:00 MHDA- 2019/02/08 06:00 CRDT- 2018/03/02 06:00 PHST- 2018/03/02 06:00 [pubmed] PHST- 2019/02/08 06:00 [medline] PHST- 2018/03/02 06:00 [entrez] AID - 10.1089/ten.TEA.2017.0462 [doi] PST - ppublish SO - Tissue Eng Part A. 2018 Aug;24(15-16):1283-1292. doi: 10.1089/ten.TEA.2017.0462. Epub 2018 Apr 10.