Human umbilical cord mesenchymal stem cells protect MC3T3-E1 osteoblasts from dexamethasone-induced apoptosis via induction of the Nrf2-ARE signaling pathway
Objective: To investigate the protective effect human umbilical cord mesenchymal stem cells (hUC-MSCs) have on Dexamethasone (Dex)-induced apoptosis in osteogenesis via the Nrf2-ARE signaling pathway. Methods: Glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH) was developed in rats t...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2024-12-01
|
| Series: | Regenerative Therapy |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S235232042400021X |
| _version_ | 1827246287393652736 |
|---|---|
| author | Chen Qiu Zhaowen Li Puji Peng |
| author_facet | Chen Qiu Zhaowen Li Puji Peng |
| author_sort | Chen Qiu |
| collection | DOAJ |
| description | Objective: To investigate the protective effect human umbilical cord mesenchymal stem cells (hUC-MSCs) have on Dexamethasone (Dex)-induced apoptosis in osteogenesis via the Nrf2-ARE signaling pathway. Methods: Glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH) was developed in rats through the administration of lipopolysaccharide and methylprednisolone. The incidence of femoral head necrosis, cavity notch, apoptosis of osteoblasts, and bone density were observed by HE staining, TUNEL staining, and Micro-CT. HUC-MSCs were co-cultured with mouse pre-osteoblast MC3T3-E1. The survival rate of osteoblasts was determined by CCK8, and apoptosis and ROS levels of osteoblasts were determined by flow cytometer. The viability of antioxidant enzymes SOD, GSH-Px, and CAT was analyzed by biochemistry. Nrf2 expression levels and those of its downstream proteins and apoptosis-related proteins were analyzed by Western blotting. Results: In rats, hUC-MSCs can reduce the rates of empty bone lacuna and osteoblast apoptosis that are induced by glucocorticoids (GCs), while reducing the incidence of GC-ONFH. hUC-MSCs can significantly improve the survival rate and antioxidant SOD, GSH-Px, and CAT activity of MC3T3-E1 cells caused by Dex, and inhibit apoptosis and oxidative stress levels. In addition, hUC-MSCs can up-regulate the expression of osteoblast antioxidant protein Nrf2 and its downstream protein HO-1, NQO-1, GCLC, GCLM, and apoptosis-related protein bcl-2, while also down-regulating the expression of apoptosis-related protein bax, cleaved caspase-3, cleaved caspase-9, and cytochrome C in MC3T3-E1 cells. hUC-MSCs improve the ability of MC3T3-E1 cells to mineralize to osteogenesis. However, the promoting effects of hUC-MSCs were abolished following the blocking of the Nrf2-ARE signaling pathway for osteoblasts. Conclusion: The results reveal that hUC-MSCs can reduce Dex-induced apoptosis in osteoblasts via the Nrf2-ARE signaling pathway. |
| first_indexed | 2024-03-07T14:01:11Z |
| format | Article |
| id | doaj.art-7b8e8f086d0a46c197911fcfa892c3d8 |
| institution | Directory Open Access Journal |
| issn | 2352-3204 |
| language | English |
| last_indexed | 2025-03-21T22:57:34Z |
| publishDate | 2024-12-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Regenerative Therapy |
| spelling | doaj.art-7b8e8f086d0a46c197911fcfa892c3d82024-05-23T04:56:12ZengElsevierRegenerative Therapy2352-32042024-12-0127111Human umbilical cord mesenchymal stem cells protect MC3T3-E1 osteoblasts from dexamethasone-induced apoptosis via induction of the Nrf2-ARE signaling pathwayChen Qiu0Zhaowen Li1Puji Peng2Department of Sports Medicine, Xiangyang Hospital of Traditional Chinese Medicine [Xiangyang Institute of Traditional Chinese Medicine], Xiangyang, 441000, ChinaDepartment of Sports Medicine, The Affiliated Hospital of Wuhan Sports University, Wuhan, 430000, ChinaDepartment of Orthopedics, Henan Provincial People's Hospital, Zhengzhou, 450003, China; Corresponding author.Objective: To investigate the protective effect human umbilical cord mesenchymal stem cells (hUC-MSCs) have on Dexamethasone (Dex)-induced apoptosis in osteogenesis via the Nrf2-ARE signaling pathway. Methods: Glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH) was developed in rats through the administration of lipopolysaccharide and methylprednisolone. The incidence of femoral head necrosis, cavity notch, apoptosis of osteoblasts, and bone density were observed by HE staining, TUNEL staining, and Micro-CT. HUC-MSCs were co-cultured with mouse pre-osteoblast MC3T3-E1. The survival rate of osteoblasts was determined by CCK8, and apoptosis and ROS levels of osteoblasts were determined by flow cytometer. The viability of antioxidant enzymes SOD, GSH-Px, and CAT was analyzed by biochemistry. Nrf2 expression levels and those of its downstream proteins and apoptosis-related proteins were analyzed by Western blotting. Results: In rats, hUC-MSCs can reduce the rates of empty bone lacuna and osteoblast apoptosis that are induced by glucocorticoids (GCs), while reducing the incidence of GC-ONFH. hUC-MSCs can significantly improve the survival rate and antioxidant SOD, GSH-Px, and CAT activity of MC3T3-E1 cells caused by Dex, and inhibit apoptosis and oxidative stress levels. In addition, hUC-MSCs can up-regulate the expression of osteoblast antioxidant protein Nrf2 and its downstream protein HO-1, NQO-1, GCLC, GCLM, and apoptosis-related protein bcl-2, while also down-regulating the expression of apoptosis-related protein bax, cleaved caspase-3, cleaved caspase-9, and cytochrome C in MC3T3-E1 cells. hUC-MSCs improve the ability of MC3T3-E1 cells to mineralize to osteogenesis. However, the promoting effects of hUC-MSCs were abolished following the blocking of the Nrf2-ARE signaling pathway for osteoblasts. Conclusion: The results reveal that hUC-MSCs can reduce Dex-induced apoptosis in osteoblasts via the Nrf2-ARE signaling pathway.http://www.sciencedirect.com/science/article/pii/S235232042400021XHuman umbilical cord mesenchymal stem cellDexamethasoneNrf2-ARE signaling pathwayApoptosisOxidative stress |
| spellingShingle | Chen Qiu Zhaowen Li Puji Peng Human umbilical cord mesenchymal stem cells protect MC3T3-E1 osteoblasts from dexamethasone-induced apoptosis via induction of the Nrf2-ARE signaling pathway Regenerative Therapy Human umbilical cord mesenchymal stem cell Dexamethasone Nrf2-ARE signaling pathway Apoptosis Oxidative stress |
| title | Human umbilical cord mesenchymal stem cells protect MC3T3-E1 osteoblasts from dexamethasone-induced apoptosis via induction of the Nrf2-ARE signaling pathway |
| title_full | Human umbilical cord mesenchymal stem cells protect MC3T3-E1 osteoblasts from dexamethasone-induced apoptosis via induction of the Nrf2-ARE signaling pathway |
| title_fullStr | Human umbilical cord mesenchymal stem cells protect MC3T3-E1 osteoblasts from dexamethasone-induced apoptosis via induction of the Nrf2-ARE signaling pathway |
| title_full_unstemmed | Human umbilical cord mesenchymal stem cells protect MC3T3-E1 osteoblasts from dexamethasone-induced apoptosis via induction of the Nrf2-ARE signaling pathway |
| title_short | Human umbilical cord mesenchymal stem cells protect MC3T3-E1 osteoblasts from dexamethasone-induced apoptosis via induction of the Nrf2-ARE signaling pathway |
| title_sort | human umbilical cord mesenchymal stem cells protect mc3t3 e1 osteoblasts from dexamethasone induced apoptosis via induction of the nrf2 are signaling pathway |
| topic | Human umbilical cord mesenchymal stem cell Dexamethasone Nrf2-ARE signaling pathway Apoptosis Oxidative stress |
| url | http://www.sciencedirect.com/science/article/pii/S235232042400021X |
| work_keys_str_mv | AT chenqiu humanumbilicalcordmesenchymalstemcellsprotectmc3t3e1osteoblastsfromdexamethasoneinducedapoptosisviainductionofthenrf2aresignalingpathway AT zhaowenli humanumbilicalcordmesenchymalstemcellsprotectmc3t3e1osteoblastsfromdexamethasoneinducedapoptosisviainductionofthenrf2aresignalingpathway AT pujipeng humanumbilicalcordmesenchymalstemcellsprotectmc3t3e1osteoblastsfromdexamethasoneinducedapoptosisviainductionofthenrf2aresignalingpathway |