Secretion of IL-6 and IL-8 in the senescence of bone marrow mesenchymal stem cells is regulated by autophagy via FoxO3a

Zheng, Yong; Wu, Shangrong; Ke, Haiqiang; Peng, Shanshan; Hu, Chengjun

doi:10.1016/j.exger.2022.112062

Cited by 8 publications

(7 citation statements)

References 39 publications

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“…As is well known, the p21 and p53 proteins can constitute a G1 cell cycle checkpoint, checking for sites of DNA damage during the G1 phase and monitoring genomic integrity. Concurrently, the p16 protein inhibits the activity of CDK4 and ultimately prevents cells from entering the S phase, resulting in cell cycle arrest and senescence [34][35][36]. In the present study, the activation of senescence-related protein pathways p16 and p21 was observed in irradiated OCYs, suggesting that IR is sufficient to activate both the p21-Rb and p16-Rb signaling pathways, thus inducing cellular senescence.…”

Section: Discussionsupporting

confidence: 51%

C-C Motif Chemokine Ligand 5 (CCL5) Promotes Irradiation-Evoked Osteoclastogenesis

Wang,

Zhao,

et al. 2023

IJMS

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The imbalance that occurs in bone remodeling induced by irradiation (IR) is the disruption of the balance between bone formation and bone resorption. In this study, primary osteocytes (OCYs) of femoral and tibial origin were cultured and irradiated. It was observed that irradiated OCY showed extensive DNA damage, which led to the initiation of a typical phenotype of cellular senescence, including the secretion of senescence-associated secretory phenotype (SASP), especially the C-C motif chemokine ligand 5 (CCL5). In order to explore the regulation of osteoclastogenic potential by IR-induced senescent OCYs exocytosis factor CCL5, the conditioned medium (CM) of OCYs was co-cultured with RAW264.7 precursor cells. It was observed that in the irradiated OCY co-cultured group, the migration potential increased compared with the vehicle culture group, accompanied by an enhancement of typical mature OCs; the expression of the specific function of enzyme tartrate-resistant acid phosphatase (TRAP) increased; and the bone-destructive function was enhanced. However, a neutralizing antibody to CCL5 could reverse the extra-activation of osteoclastogenesis. Accordingly, the overexpression of p-STAT3 in irradiated OCY was accompanied by CCL5. It was concluded that CCL5 is a potential key molecule and the interventions targeting CCL5 could be a potential strategy for inhibiting osteoclastogenesis and restoring bone remodeling.

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Section: Discussionsupporting

confidence: 51%

C-C Motif Chemokine Ligand 5 (CCL5) Promotes Irradiation-Evoked Osteoclastogenesis

Wang,

Zhao,

et al. 2023

IJMS

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“…Those cytokines influence either cell proliferation or senescence. Interestingly, MSCs under fructose significantly release more senescence markers such as IL4, IL8, and IL10 21–24 . Notably, the increase of GM-CSF is associated with the differentiation into monocyte lineage 25 .…”

Section: Resultsmentioning

confidence: 99%

“…Interestingly, we showed that IL4, IL8, and IL10 were increased in the fructose containing medium along with the reduction in GDF15, a growth factor that supports proliferation 26 . These three interleukins are associated with senescence phenotype 21,24 . Hence, fructose exerts stress on stem cells associated with increased Hif1a and activation of senescence associated phenotype.…”

Section: Discussionmentioning

confidence: 99%

Fructose vs. Glucose: Modulating Stem Cell Growth and Function Through Sugar Supplementation

Elsaid,

Wu,

Tee

2024

Preprint

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In multicellular organisms, stem cells are impacted by microenvironmental resources such as nutrient availability and oxygen tension for their survival, growth, and differentiation. However, the accessibility of these resources in the pericellular environment greatly varies from organ to organ. This divergence in resource availability leads to variations in the potency and differentiation potential of stem cells. Moreover, hexose and oxygen levels modulate cytokine production which is crucial for cell-cell communication as well as growth, and differentiation of stem cell. Hence, this study aims to explore the distinct effects of glucose and fructose, as well as different oxygen tensions, on the growth dynamics, cytokine production, and differentiation of stem cells.

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“…IL-8, another important member of the SASP family, exhibits an expression pattern similar to that of IL-6. Chondrocytes from patients with OA highly express both IL-6 and IL-8, whereas forkhead box O (FoxO) 3a knockdown reduces IL-6 and IL-8 production ( 57 ). Notably, IL-6 levels are correlated with the senescence index ( 58 ).…”

Section: Senescence-associated Secretory Phenotype (Sasp) In the Skel...mentioning

confidence: 99%

Cellular senescence in skeletal disease: mechanisms and treatment

He,

Hu,

Zhang

et al. 2023

Cell Mol Biol Lett

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The musculoskeletal system supports the movement of the entire body and provides blood production while acting as an endocrine organ. With aging, the balance of bone homeostasis is disrupted, leading to bone loss and degenerative diseases, such as osteoporosis, osteoarthritis, and intervertebral disc degeneration. Skeletal diseases have a profound impact on the motor and cognitive abilities of the elderly, thus creating a major challenge for both global health and the economy. Cellular senescence is caused by various genotoxic stressors and results in permanent cell cycle arrest, which is considered to be the underlying mechanism of aging. During aging, senescent cells (SnCs) tend to aggregate in the bone and trigger chronic inflammation by releasing senescence-associated secretory phenotypic factors. Multiple signalling pathways are involved in regulating cellular senescence in bone and bone marrow microenvironments. Targeted SnCs alleviate age-related degenerative diseases. However, the association between senescence and age-related diseases remains unclear. This review summarises the fundamental role of senescence in age-related skeletal diseases, highlights the signalling pathways that mediate senescence, and discusses potential therapeutic strategies for targeting SnCs. Graphical Abstract

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Secretion of IL-6 and IL-8 in the senescence of bone marrow mesenchymal stem cells is regulated by autophagy via FoxO3a

Cited by 8 publications

References 39 publications

C-C Motif Chemokine Ligand 5 (CCL5) Promotes Irradiation-Evoked Osteoclastogenesis

C-C Motif Chemokine Ligand 5 (CCL5) Promotes Irradiation-Evoked Osteoclastogenesis

Fructose vs. Glucose: Modulating Stem Cell Growth and Function Through Sugar Supplementation

Cellular senescence in skeletal disease: mechanisms and treatment

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