A Neuroprotective Bovine Colostrum Attenuates Apoptosis in Dexamethasone-Treated MC3T3-E1 Osteoblastic Cells.

Sagrario Martin-Aragon,Yiannis Koutedakis,Carlos Raposo,Eirini K Kydonaki,Paloma Bermejo-Bescós,Paraskevi Gkiata,Georgia Ntina,Franklim Marques,Andres E Carrillo,Tânia Amorim,Juana Benedí

doi:10.3390/ijms221910195

Abstract

Glucocorticoid-induced osteoporosis (GIO) is one of the most common secondary forms of osteoporosis. GIO is partially due to the apoptosis of osteoblasts and osteocytes. In addition, high doses of dexamethasone (DEX), a synthetic glucocorticoid receptor agonist, induces neurodegeneration by initiating inflammatory processes leading to neural apoptosis. Here, a neuroprotective bovine colostrum against glucocorticoid-induced neuronal damage was investigated for its anti-apoptotic activity in glucocorticoid-treated MC3T3-E1 osteoblastic cells. A model of apoptotic osteoblastic cells was developed by exposing MC3T3-E1 cells to DEX (0–700 μM). Colostrum co-treated with DEX was executed at 0.1–5.0 mg/mL. Cell viability was measured for all treatment schedules. Caspase-3 activation was assessed to determine both osteoblast apoptosis under DEX exposure and its potential prevention by colostrum co-treatment. Glutathione reduced (GSH) was measured to determine whether DEX-mediated oxidative stress-driven apoptosis is alleviated by colostrum co-treatment. Western blot was performed to determine the levels of p-ERK1/2, Bcl-XL, Bax, and Hsp70 proteins upon DEX or DEX plus colostrum exposure. Colostrum prevented the decrease in cell viability and the increase in caspase-3 activation and oxidative stress caused by DEX exposure. Cells, upon colostrum co-treated with DEX, exhibited higher levels of p-ERK1/2 and lower levels of Bcl-XL, Bax, and Hsp70. Our data support the notion that colostrum may be able to reduce DEX-induced apoptosis possibly via the activation of the ERK pathway and modulation of the Hsp70 system. We provided preliminary evidence on how bovine colostrum, as a complex and multi-component dairy product, in addition to its neuroprotective action, may affect osteoblastic cell survival undergoing apoptosis.

Highlights

Osteoporosis is a systemic degenerative disease during aging which is associated with increased fragility and fracture risk of bone [1]
Based on the fact that high doses of dexamethasone (DEX) induce neurodegeneration and that glucocorticoid-induced osteoporosis (GIO) is one of the most common secondary and iatrogenic forms of osteoporosis, the present study hypothesized that neuroprotective bovine colostrum against DEX-induced neuronal damage may exert protective effects against glucocorticoid-induced osteoblast injury
Glucocorticoid-induced damage in the SH-SY5Y human neuroblastoma cell line was generated by long-term exposure to DEX

Summary

Introduction

Osteoporosis is a systemic degenerative disease during aging which is associated with increased fragility and fracture risk of bone [1]. Younger populations may demonstrate increased fragility and fracture risk of bone [3,4]. It has been shown that low bone density and osteoporosis may be related to dementia and Alzheimer’s disease (AD) in postmenopausal women [7,8]. Glucocorticoids, used as a treatment of chronic diseases based on their anti-inflammatory, immune-modulatory, and antiproliferative properties, are associated with serious side effects, including osteoporosis [9]. The toxicity of dexamethasone appears to be based on its toxic effect on neuronal function, and on impairment of the nervous system leading to neuronal death processes [11]

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