Tabersonine ameliorates osteoblast apoptosis in rats with dexamethasone-induced osteoporosis by regulating the Nrf2/ROS/Bax signalling pathway
Authors: Lijun Gan
Nan Li
Xi Sun
Shuyi Sun
Na Li
Journal: AMB Express (2020)
Discipline: MICROBIOLOGY
Keywords: Dexamethasone; Inflammation; Osteoblast; Osteoporosis; Oxidative stress
Affiliations: Department of Neonatology, First Hospital of Jilin University, No. 71 Xinmin Street, Chaoyang District, Changchun, 130021, Jilin, China., Department of Ultrasonography, Jilin Provincial People's Hospital, Changchun, 130000, Jilin, China., Department of Neonatology, First Hospital of Jilin University, No. 71 Xinmin Street, Chaoyang District, Changchun, 130021, Jilin, China. .

Abstract:  We explored how tabersonine (Tab) protected against dexamethasone (Dex)-induced osteoporosis. Osteoblasts were treated with Dex (100 µM) with or without Table (5 or 10 µM). We measured cell viability, alkaline phosphatase (ALP) activity, and mitochondrial superoxide and reactive oxygen species levels. We used flow cytometry to explore the effects of Tab on mitochondrial membrane potential and osteoblast apoptosis. We used RT-PCR and western blotting to examine the effect of Tab on protein expression. We evaluated the effects of Tab on bone histopathology and bone mineral density in rats with Dex-induced osteoporosis. Tab increased cell viability and ALP activity, and reduced the mitochondrial superoxide, reactive oxygen species and matrix metalloproteinase levels and osteoblast apoptosis. Tab significantly reduced the levels of nuclear factor erythroid 2-related factor 2 (Nrf2), haem oxygenase-1 and NAD(P)H quinone dehydrogenase 1. Moreover, it increased the levels of mRNAs encoding runt-related transcription factor 2, bone morphogenetic protein-2 and osterix. These data suggest that Tab ameliorates Dex-induced osteoporosis by regulating the Nrf2 signalling pathway. 

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 - *[left]* Fig 8. - *[middle]* Fig 5 from  Pristimerin inhibits neuronal inflammation and protects cognitive function in mice with sepsis-induced brain injuries by regulating PI3K Akt signalling ([Xue et al 2021] ). - *[right]* Fig 4A from  Fuscoside Attenuates Bone Loss in Bone Defects by Regulating The Rankl Nlrp3 Opg Pathway in Rats ([Liu Wang 2021] ). ![file] Red and purple boxes are for comparison with - *[left]* Fig 6 from  A miR-1275 mimic protects myocardiocyte apoptosis by regulating the Wnt NF-u03baB pathway in a rat model of myocardial ischemiau2013reperfusion-induced myocardial injury ([Jiang et al 2020] ) **[retracted]**. - *[right]* Fig 3 from  MiR-1906 Attenuates Neuropathic Pain in Rats by Regulating the TLR4 mTOR Akt Signaling Pathway ([Fang et al 2019] ). ![file] , 
 *[left]* Fig 4,  Effect of tabersonine on the mitochondrial membrane potential of osteoblasts treated with dexamethasone . ![file] Panels appear to come from *[right]* Fig 2A of  Gastrodin alleviates glucocorticoid induced osteoporosis in rats via activating the Nrf2 signaling pathways ([Liu et al 2018] ).  GSTD improved MOMP in DEX induced injury of mitochondria via Nrf2 pathway in primary osteoblasts, performed following JC-1 double fluorescent dye staining. (A) Cells were pretreated with GSTD (1, 5 u03bcM) for 2 h prior to incubation with DEX (100 u03bcM) for 24 h, followed by flow cytometry detection. GSTD alleviated DEX induced mitochondrial oxidative stress via Nrf2 pathway by cytometry of mitoSOXu2122 Red staining . , 
 *[left]* Fig 9a,  Histopathological bone changes revealed by H E staining . Panels come from *[right]* Fig 8A of  Gastrodin protects MC3T3-E1 osteoblasts from dexamethasone-induced cellular dysfunction and promotes bone formation via induction of the NRF2 signaling pathway ([Liu et al 2016] ). ![file] ,