H₂O₂ Damages the Stemness of Rat Bone Marrow-Derived Mesenchymal Stem Cells: Developing a “Stemness Loss” Model

Deng, Xueqing; Jing, Doudou; Liang, Hang; Zheng, Dong; Shao, Zengwu

doi:10.12659/msm.914011

Cited by 4 publications

(1 citation statement)

References 33 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies have strongly indicated that BMSCs can effectively promote cartilage erosion regeneration in OA by not only differentiating into cartilage-forming chondrocytes but also modulating the behavior of subchondral bone 5 . However, the abnormal microenvironment of OA characterized by stress conditions, such as inflammation 6 and oxidative stress 7 , 8 , reduces the survival capacity of BMSCs. Moreover, high pro-inflammatory cytokine levels inhibit BMSCs osteogenesis 9 .…”

Section: Introductionmentioning

confidence: 99%

GABARAP ameliorates IL-1β-induced inflammatory responses and osteogenic differentiation in bone marrow-derived stromal cells by activating autophagy

Guo

2021

Sci Rep

View full text Add to dashboard Cite

Bone mesenchymal stem cells (BMSCs) are the most commonly investigated progenitor cells in bone defect repair and osteoarthritis subchondral bone regeneration; however, these studies are limited by complex inflammatory conditions. In this study, we investigated whether pro-autophagic γ-aminobutyric acid receptor-associated protein (GABARAP) promotes BMSCs proliferation and osteogenic differentiation by modulating autophagy in the presence or absence of interleukin-1 beta (IL-1β) in vitro. The expression levels of all relevant factors were evaluated by qRT-PCR or western blotting where appropriate. BMSCs differentiation were assessed by Alizarin Red, alkaline phosphatase, safranin O, and Oil Red O staining. Furthermore, the interactions between autophagy and osteogenic differentiation were investigated by co-treatment with the autophagy inhibitor 3-methyladenine (3-MA). As the results, we found that treatment with recombinant human His6-GABARAP protein promoted cell proliferation, inhibited apoptosis, and reduced ROS generation by increasing autophagic activity, particularly when co-cultured with IL-1β. Moreover, His6-GABARAP could effectively increase the osteogenic differentiation of BMSCs. The expression levels of inflammatory factors were significantly decreased by His6-GABARAP treatment, whereas its protective effects were attenuated by 3-MA. This study demonstrates that GABARAP maintains BMSCs survival and strengthens their osteogenic differentiation in an inflammatory environment by upregulating mediators of the autophagy pathway.

show abstract

Section: Introductionmentioning

confidence: 99%

GABARAP ameliorates IL-1β-induced inflammatory responses and osteogenic differentiation in bone marrow-derived stromal cells by activating autophagy

Guo

2021

Sci Rep

View full text Add to dashboard Cite

show abstract

Garcinol prevents oxidative stress-induced bone loss and dysfunction of BMSCs through NRF2-antioxidant signaling

Zou,

Chen,

Fan

et al. 2024

Cell Death Discov.

View full text Add to dashboard Cite

There are multiple published data showing that excessive oxidative stress contributes to bone loss and even bone tissue damage, and it is also correlated with the pathophysiology of bone degenerative diseases, including osteoporosis (OP). Garcinol, a polyisoprenylated benzophenone derivative, has been recently established as an anti-oxidant agent. However, it remains elusive whether Garcinol protects bone marrow mesenchymal stem cells (BMSCs) and bone tissue from oxidative stress-induced damage. Here, we explored the potential effects of Garcinol supplementation in ameliorating oxidative stimulation-induced dysfunction of BMSCs and bone loss in osteoporotic mice. In this study, we verified that Garcinol exerted potent protective functions in the hydrogen peroxide (H2O2)-induced excessive oxidative stress and dysfunction of BMSCs. Besides, Garcinol was also identified to improve the reduced bone mass and abnormal lineage commitment of BMSCs in the condition of OP by suppressing the oxidative stimulation. Subsequent analysis revealed that nuclear factor erythroid 2-related factor 2 (NRF2) might be a key regulator in the sheltering effects of Garcinol on the H2O2-regulated oxidative stress, and the protective functions of Garcinol was mediated by NRF2-antioxidant signaling. Collectively, Garcinol prevented oxidative stress-related BMSC damage and bone loss through the NRF2-antioxidant signaling, which suggested the promising therapeutic values of Garcinol in the treatment of oxidative stress-related bone loss. Therefore, Garcinol might contribute to treating OP.

show abstract

Redox signaling regulates the skeletal tissue development and regeneration

Zhang

Hao

Hong³

et al. 2023

Biotechnology and Genetic Engineering Reviews

View full text Add to dashboard Cite

H₂O₂ Damages the Stemness of Rat Bone Marrow-Derived Mesenchymal Stem Cells: Developing a “Stemness Loss” Model

Cited by 4 publications

References 33 publications

GABARAP ameliorates IL-1β-induced inflammatory responses and osteogenic differentiation in bone marrow-derived stromal cells by activating autophagy

GABARAP ameliorates IL-1β-induced inflammatory responses and osteogenic differentiation in bone marrow-derived stromal cells by activating autophagy

Garcinol prevents oxidative stress-induced bone loss and dysfunction of BMSCs through NRF2-antioxidant signaling

Redox signaling regulates the skeletal tissue development and regeneration

Contact Info

Product

Resources

About