BDNF promoted osteoblast migration and fracture healing by up‐regulating integrin β1 via TrkB‐mediated ERK1/2 and AKT signalling

Zhang, Zitao; Hu, Polu; Wang, Zhen; Qiu, Xusheng; Chen, Yixin

doi:10.1111/jcmm.15704

Cited by 18 publications

(16 citation statements)

References 37 publications

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“…BDNF promoted multiple cells proliferation including trophoblastic cell [ 32 ], oligodendrocyte precursors [ 33 ] and schwann cells [ 34 ]. Zhang et al [ 35 ] also found that BDNF could promoting osteoblast migration through ERK1/2 and Akt signaling pathway. Borghesani et al [ 36 ] revealed that BDNF is directly motogenic for granule cells and provides a directional cue promoting migration from the granule cell layer to the internal granule cell layer.…”

Section: Discussionmentioning

confidence: 99%

Localized delivery of brain-derived neurotrophic factor from PLGA microspheres promotes peripheral nerve regeneration in rats

Fan

Zhang

et al. 2022

J Orthop Surg Res

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Background Repair of peripheral nerve defect presents a considerable challenge for reconstructive surgeons. The aim of this study is to develop a brain-derived neurotrophic factor (BDNF) from poly(D,L-lactide-co-glycolide) (PLGA) microspheres for the treatment of the peripheral nerve defect. Method BDNF microspheres were prepared by using an oil-in-water emulsification-solvent evaporation method. The morphology, particle size, encapsulation efficiency, drug loading and sustained release performance of microspheres was observed and calculated. Adipose mesenchymal stem cells (ADSCs) were isolated and expanded. ADSCs were divided into four groups: control, BDNF, blank microsphere and BDNF microsphere groups. Cell count kit-8 (CCK-8) assays were used to assess cell proliferation. Cell migration was determined by Transwell assays. Twenty-eight male Sprague–Dawley rats underwent transection damage model on the right sciatic nerve. The wet weight ratio of the gastrocnemius muscle was calculated by comparing the weight of the gastrocnemius muscle from the operated side to that of the normal side. Neuroelectrophysiological testing was performed to assess nerve function recovery. Nerve regeneration was evaluated by histological analysis and immunohistochemical staining. Results The microspheres were spherical and had uniform size (46.38 ± 1.00 μm), high encapsulation efficiency and high loading capacity. In vitro release studies showed that BDNF-loaded microspheres had good sustained release characteristics. The duration of BDNF release was extended to more than 50 days. BDNF or BDNF microsphere promote the proliferation and migration of ADSCs than control group (P < 0.05). Compared with control group, BDNF significantly decreased the nerve conduction velocity (NCV) and compound amplitude (AMP) (P < 0.05). The nerve fibers in the BDNF microsphere group were closely arranged and uniformly distributed than control group. Conclusion BDNF/PLGA sustained-release microsphere could promote the migration of ADSCs and promoted neural differentiation of ADSCs. Moreover, BDNF/PLGA sustained-release microsphere ameliorated nerve conduction velocity and prevented neuralgic amyotrophy.

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Section: Discussionmentioning

confidence: 99%

Localized delivery of brain-derived neurotrophic factor from PLGA microspheres promotes peripheral nerve regeneration in rats

Fan

Zhang

et al. 2022

J Orthop Surg Res

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“…Besides, the promotion effect of BDNF on osteoblast migration and fracture healing is also via TrkB. The specific inhibitor for Trks, K252a, can suppress BDNF-induced cell migration, integrin β1 expression and activation of ERK1/2 and AKT signaling pathways (Zitao Zhang et al, 2020). We thus hypothesized that TrkB is the link between 7,8-DHF and Wnt/β-catenin reinforcement during osteogenic differentiation.…”

Section: Discussionmentioning

confidence: 99%

“…Afterward, some researches confirmed that BDNF plays a positive role in accelerating bone union ( Kauschke et al, 2018a ; Kauschke et al, 2018b ; Liu et al, 2018 ). Recently, a study provided further understanding for the underlying mechanism of BDNF in fracture healing that BDNF contributed to MC3T3-E1 migration and increased the expression level of integrin β1 ( Zhang et al, 2020 ). Considering the fact that 7,8-DHF mimics so many aspects of BDNF, we hypothesized that there may be a regulatory network involving 7,8-DHF and bone remodeling.…”

Section: Discussionmentioning

confidence: 99%

“…7,8-DHF is now extensively validated in various biochemical and cellular systems. It has been shown that BDNF could promote osteoblast differentiation, migration, and fracture healing ( Kilian et al, 2014 ; Liu et al, 2018 ; Zhang et al, 2020 ; Zhang et al, 2017 ). Recently, we found that 7,8-DHF at the dose of 10 mg/kg·BW resulted in a marked increase in bone mineral density (BMD) irrespective of dietary conditions in female mice ( Zhao et al, 2021 ).…”

Section: Introductionmentioning

confidence: 99%

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7,8-Dihydroxyflavone modulates bone formation and resorption and ameliorates ovariectomy-induced osteoporosis

Zhao

Han

et al. 2021

eLife

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Imbalances in bone formation and resorption cause osteoporosis. Mounting evidence supports that brain-derived neurotrophic factor (BDNF) implicates in this process. 7,8-dihydroxyflavone (7,8-DHF), a plant-derived small molecular TrkB agonist, mimics the functions of BDNF. We show that both BDNF and 7,8-DHF promoted the proliferation, osteogenic differentiation and mineralization of MC3T3-E1 cells. These effects might be attributed to the activation of the Wnt/β-catenin signaling pathway as the expression of cyclin D1, phosphorylated-glycogen synthase kinase-3β (p-GSK3β), β-catenin, Runx2, Osterix and osteoprotegerin (OPG) were all significantly up-regulated. Knockdown of β-catenin restrained the up-regulation of Runx2 and Osterix stimulated by 7,8-DHF. In particular, blocking TrkB by its specific inhibitor K252a suppressed 7,8-DHF-induced osteoblastic proliferation, differentiation and expression of osteoblastogenic genes. Moreover, BDNF and 7,8-DHF repressed osteoclastic differentiation of RAW264.7 cells. The transcription factor c-fos and osteoclastic genes such as tartrate-resistant acid phosphatase (TRAP), matrix metalloprotein-9 (MMP-9), Adamts5 were inhibited by 7,8-DHF. More importantly, 7,8-DHF attenuated bone loss, improved trabecular microarchitecture, tibial biomechanical properties and bone biochemical indexes in an ovariectomy (OVX) rat model. The current work highlights the dual regulatory effects that 7,8-DHF exerts on bone remodeling.

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“…[ 13 ] BDNF is an important regulator of nervous system, [ 14 , 15 ] and also participates in the regulation of bone tissues. [ 16 , 17 ] Nose and coworkers found that serum BDNF level was positively correlated with BMD, and that it was elevated by estradiol therapy in female osteoporosis patients. [ 18 ] BDNF knockout could inhibit osteoblast differentiation.…”

Section: Introductionmentioning

confidence: 99%

Genetic association between bone mineral density and the fracture of distal radius

Li¹,

Fu²,

Gao³

et al. 2021

Medicine

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Low bone mineral density (BMD) was significantly related to the fracture of distal radius. Serum brain-derived neurotrophic factor (BDNF) level was closely related to BMD in spine and osteoporotic fractures. In this study, we aimed to explore the association of BDNF polymorphisms (rs6265 and rs7124442) with BMD and the fracture of distal radius. This retrospective study included 152 patients with distal radius fractures and 148 healthy controls. BDNF polymorphisms were detected via TaqMan allelic discrimination assay. BMD was evaluated through X-ray. Difference in features between cases and controls were compared adopting Chi-square test or t test. The associations of BDNF polymorphisms with fracture risk of distal radius and BMD were assessed employing χ 2 test and expressed by odd ratios (ORs) with 95% confidence intervals (95% CIs). BMD was significantly decreased in patients with the fracture of distal radius than in healthy controls. The polymorphism rs6265 significantly increased the risk of distal radius fracture (adjustment: GA: OR = 1.724, 95%CI = 1.003 –2.951, P = .049; GG: OR = 2.415, 95%CI = 1.0219 –3.674, P = .005). Moreover, rs6265 genotypes GA (OR = 4.326, 95%CI = 1.725 –11.896, P = .003) and GG (OR = 13.285, 95%CI = 3.659 –51.072, P = .001) significantly increased BMD reduction. However, BDNF polymorphism rs7124442 had no obvious correlation with BMD or fracture risk. BMD was associated with BDNF rs6265 polymorphism. BDNF polymorphism rs6265 could elevate the risk of osteoporosis and distal radius fracture.

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BDNF promoted osteoblast migration and fracture healing by up‐regulating integrin β1 via TrkB‐mediated ERK1/2 and AKT signalling

Cited by 18 publications

References 37 publications

Localized delivery of brain-derived neurotrophic factor from PLGA microspheres promotes peripheral nerve regeneration in rats

Localized delivery of brain-derived neurotrophic factor from PLGA microspheres promotes peripheral nerve regeneration in rats

7,8-Dihydroxyflavone modulates bone formation and resorption and ameliorates ovariectomy-induced osteoporosis

Genetic association between bone mineral density and the fracture of distal radius

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