BDNF regulates the expression and secretion of VEGF from osteoblasts via the TrkB/ERK1/2 signaling pathway during fracture healing

Zhang,Zitao; Zhang,Yan; Zhou,Zhengnan; Shi,Hongfei; Qiu,Xusheng; Xiong,Jin; Chen,Yixin

doi:10.3892/mmr.2017.6110

BDNF regulates the expression and secretion of VEGF from osteoblasts via the TrkB/ERK1/2 signaling pathway during fracture healing

Authors:
- Zitao Zhang
- Yan Zhang
- Zhengnan Zhou
- Hongfei Shi
- Xusheng Qiu
- Jin Xiong
- Yixin Chen
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Affiliations: Department of Orthopedics, The Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu 210008, P.R. China
Published online on: January 12, 2017 https://doi.org/10.3892/mmr.2017.6110
Pages: 1362-1367

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Abstract

Brain‑derived neurotrophic factor (BDNF), a member of the neurotropic family, is expressed in osteoblast‑like cells of a fracture callus, however, its role in fracture healing remains to be fully elucidated. Osteoblasts isolated from Sprague Dawley rats were stimulated by BDNF in a dose‑ and time‑dependent manner. Immunoblotting and immunofluorescence was used to detect the expression and distribution of targeted proteins. The concentration of vascular endothelial growth factor (VEGF) released in medium was determined using an ELISA. PD98059 and K252a were used to investigate the signaling pathways that may be involved. The present study demonstrated that BDNF was involved in fracture repair by controlling the expression and secretion of VEGF from osteoblasts, which predominantly drives angiogenesis during fracture healing. Tropomyosin‑related kinase B (TrkB), the specific receptor of BDNF, was shown to be expressed at high levels in the osteoblasts. Following BDNF stimulation, TrkB and extracellular signal‑regulated kinase 1/2 (ERK1/2) were rapidly activated. The inhibition of TrkB by K252a decreased the expression and secretion of VEGF, and suppressed the phosphorylation level of ERK1/2. PD98059, an antagonist of ERK1/2, elicited the same effects on VEGF from the BDNF‑stimulated osteoblasts, however, it did not affect the phosphorylation of TrkB. In conclusion, during fracture healing, BDNF was found to stimulate the expression and secretion of VEGF from osteoblasts via the TrkB/ERK1/2 signaling pathway.

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