Irradiation-induced senescence of bone marrow mesenchymal stem cells aggravates osteogenic differentiation dysfunction via paracrine signaling

Bai, Jiangtao; Wang, Yuyang; Wang, Jianping; Zhai, Jianglong; He, Feilong; Zhu, Guoying

doi:10.1152/ajpcell.00520.2019

Cited by 41 publications

(43 citation statements)

References 38 publications

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“…Supposing that bone requires increased cell proliferation to achieve healing, our results confirmed existing findings that radiation significantly reduced the bone healing process (Stone et al, 2003;Batista et al, 2014;Rocha et al, 2017). Specifically, irradiated bone marrow-derived mesenchymal stem cells (BMSCs) have exhibited declined viability and impaired osteogenic differentiation (Bai et al, 2020;Chouinard et al, 2016), with reduced bone cell phenotype replacement (Bai et al, 2020), as observed in Group RXT.…”

Section: Discussionsupporting

confidence: 87%

“…The reduction in BMSCs post-irradiation could be one of the important causes of radiationinduced bone deterioration (Bai et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

“…These results are conflicting with others who have demonstrated improved bone regeneration (Park et al, 2019) and angiogenesis (An et al, 2019) in irradiated (12Gy single dose) calvaria defects after HBO treatment. This most probably occurred due to different experimental models, considering that damage by radiation occurs in a dose-dependent manner (Lerouxel et al, 2009;Limirio et al, 2019;Bai et al, 2020). To our knowledge, the main target for the physiological action of HBO is tissue hypoxia (Choudhury et al, 2018).…”

Section: Discussionmentioning

confidence: 99%

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Influência da oxigenação hiperbárica no reparo ósseo e organização do colágeno após radioterapia

Rocha¹,

Rezende²,

Reis³

et al. 2020

RSD

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O presente estudo teve como objetivo avaliar os efeitos da HBO no reparo ósseo após radiação ionizante, por meio da histomorfometria, tomografia computadorizada e microscopia de polarização. Vinte ratos Wistar machos foram usados. Uma dose de radiação (30 Gy) foi administrada na perna esquerda em todos os animais, e após 30 dias, defeitos ósseos foram criados em ambos os fêmures. Em seguida, 10 animais receberam sessões diárias de HBO (2,5 ATA por 90 minutos), e todos os animais foram sacrificados 5 ou 7 dias após a cirurgia. Os fêmures foram separados em 4 grupos (n = 5) para cada intervalo de tempo de eutanásia: Controle (fêmur direito: não irradiado e não HBO), RXT (fêmur esquerdo: irradiado e não HBO), HBO (fêmur direito: não-irradiado com HBO), RXT + HBO (fémur esquerdo: irradiado com HBO). A cortical óssea e os defeitos foram avaliados. Os dados foram analisados por meio dos testes de Kolmogorov-Smirnov, teste t não pareado e ANOVA com correção de Bonferroni. Valores maiores de HU e neoformação óssea foram observados nos grupos Controle e HBO, com melhora do reparo. O grupo HBO apresentou birrefringência de colágeno predominantemente amarela/laranja/vermelha na área do defeito. A HBO melhorou a reparação óssea em condições fisiológicas, com aumento dos vasos sanguíneos e formação óssea. No entanto, não foi eficiente em melhorar o reparo e a orientação do colágeno no osso após altas doses de radiação ionizante.

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Section: Discussionsupporting

confidence: 87%

“…The reduction in BMSCs post-irradiation could be one of the important causes of radiationinduced bone deterioration (Bai et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Influência da oxigenação hiperbárica no reparo ósseo e organização do colágeno após radioterapia

Rocha¹,

Rezende²,

Reis³

et al. 2020

RSD

View full text Add to dashboard Cite

show abstract

“…In another instance increasing doses of radiation induced proportional levels of senescence and gene expression for SASP markers in rat BMSCs [131]. Lipopolysaccharides have also been shown to induce senescence in alveolar bone together with the SASP factors such as Icam1, Il6, Mmp13, and TNF-alpha [132].…”

Section: Senescence Associated Secretory Phenotype (Sasp)mentioning

confidence: 99%

Skeletal Aging and Osteoporosis: Mechanisms and Therapeutics

Chandra

Rajawat

2021

IJMS

117

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Bone is a dynamic organ maintained by tightly regulated mechanisms. With old age, bone homeostasis, which is maintained by an intricate balance between bone formation and bone resorption, undergoes deregulation. Oxidative stress-induced DNA damage, cellular apoptosis, and cellular senescence are all responsible for this tissue dysfunction and the imbalance in the bone homeostasis. These cellular mechanisms have become a target for therapeutics to treat age-related osteoporosis. Genetic mouse models have shown the importance of senescent cell clearance in alleviating age-related osteoporosis. Furthermore, we and others have shown that targeting cellular senescence pharmacologically was an effective tool to alleviate age- and radiation-induced osteoporosis. Senescent cells also have an altered secretome known as the senescence associated secretory phenotype (SASP), which may have autocrine, paracrine, or endocrine function. The current review discusses the current and potential pathways which lead to a senescence profile in an aged skeleton and how bone homeostasis is affected during age-related osteoporosis. The review has also discussed existing therapeutics for the treatment of osteoporosis and rationalizes for novel therapeutic options based on cellular senescence and the SASP as an underlying pathogenesis of an aging bone.

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“…In addition, several factors derived from the accumulation of senescent cells are implicated as causal in age-related osteoporosis and imbalance of bone metabolism (21). Findings of previous studies of cellular senescence have primarily focused on stem cells (22,23). By contrast, there are a limited number of studies on post-mitotic cells, such as the terminally differentiated osteocytes (24)(25)(26).…”

Section: Introductionmentioning

confidence: 99%

Radiation induces primary osteocyte senescence phenotype and affects osteoclastogenesis in vitro

Wang

et al. 2021

Int J Mol Med

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Irradiation-induced bone remodeling imbalances arise as a consequence of the dysregulation of bone formation and resorption. due to the abundance of osteocytes, their long life and their dual-regulatory effects on both osteoblast and osteoclast function, they serve as critical coordinators of bone remolding. In the present study, femur and tibia-derived primary osteocytes were cultured and irradiated to observe the functional changes and the cellular senescence phenotype in vitro. Irradiation directly reduced cell viability, affected the crucial dendritic morphology and altered the expression of functional proteins, including upregulation of receptor activator of nuclear factor-κB ligand and sclerostin, and downregulation of osteoprotegerin. Irradiated osteocytes were shown to exhibit notable dNA damage, which resulted in the initiation of a typical cellular senescence phenotype. Furthermore, it was found that irradiation-induced prematurely senescent osteocytes stimulate molecular secretion, referred to as senescence-associated secretory phenotype (SASP), which may be involved in modulation of the bone microenvironment, including the promotion of osteoclastogenesis. Taken together, the results showed that irradiation triggered osteocyte senescence and the acquisition of an associated secretory phenotype. This further resulted in an imbalance of bone remodeling through senescent influence on proliferation, morphology and marker protein production, but also indirectly via a paracrine pathway through SASP secretion. The results of the present study may highlight the potential of SASP-targeted interventions for the management of radiation-induced bone loss.

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Irradiation-induced senescence of bone marrow mesenchymal stem cells aggravates osteogenic differentiation dysfunction via paracrine signaling

Cited by 41 publications

References 38 publications

Influência da oxigenação hiperbárica no reparo ósseo e organização do colágeno após radioterapia

Influência da oxigenação hiperbárica no reparo ósseo e organização do colágeno após radioterapia

Skeletal Aging and Osteoporosis: Mechanisms and Therapeutics

Radiation induces primary osteocyte senescence phenotype and affects osteoclastogenesis in vitro

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