Knockdown of SIRT3 perturbs protective effects of irisin against bone loss in diabetes and periodontitis

Li, Guangyue; Qin, Han; Zhou, Menglong; Zhang, Tingwei; Zhang, Yang; Ding, Huifen; Xu, Ling; Song, Jinlin

doi:10.1016/j.freeradbiomed.2023.02.023

“…Our study discovered that irisin activated SOD1 and GPx1, resulting in decreased levels of ROS in BMMSCs and protection of the mitochondrial from oxidative injury. Additionally, irisin was found to up-regulate the expression of SIRT3, an upstream factor that regulates a variety of antioxidant enzymes [39] . Consistent with our ndings, irisin has been documented to provide protection against SIRT3 down-regulation caused by oxidative stress [40] .…”

Section: Discussionmentioning

confidence: 99%

Irisin-loaded electrospun core-shell nanofibers as calvarial periosteum accelerate vascularized bone regeneration by activating the mitochondrial SIRT3 pathway

Hua

¹

,

Hou

²

,

Deng

³

et al. 2023

Preprint

0

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The scarcity of native periosteum poses a significant clinical barrier in the repair of critical-sized bone defects. The challenge of enhancing regenerative potential in bone healing is further compounded by oxidative stress at the fracture site. However, the introduction of artificial periosteum has demonstrated its ability to promote bone regeneration through the provision of appropriate mechanical support and controlled release of pro-osteogenic factors. In this study, a polylactic acid (PLLA)/hyaluronic acid (HA)-based nanofibrous membrane was fabricated using the coaxial electrospinning technique. The incorporation of irisin into the core-shell structure of PLLA/HA nanofibers (PLLA/HA@Irisin) achieved its sustained release. In vitro experiments demonstrated that the PLLA/HA@Irisin membranes exhibited favorable biocompatibility. The osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs) was improved by PLLA/HA@Irisin, as evidenced by a significant increase in alkaline phosphatase (ALP) activity and matrix mineralization. Mechanistically, PLLA/HA@Irisin significantly enhanced the mitochondrial function of BMMSCs via the activation of the sirtuin 3 antioxidant pathway. To assess the therapeutic effectiveness, PLLA/HA@Irisin membranes were implanted in situ into critical-sized calvarial defects in rats. The results at four and eight weeks post-surgery indicated that the implantation of PLLA/HA@Irisin exhibited superior efficacy in promoting vascularized bone formation, as demonstrated by the enhancement of bone matrix synthesis and the development of new blood vessels. The results of our study indicate that the electrospun PLLA/HA@Irisin nanofibers possess characteristics of a biomimetic periosteum, showing potential for effectively treating critical-sized bone defects by improving the mitochondrial function and maintaining redox homeostasis of BMMSCs.

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“…Our study discovered that irisin activated SOD1 and GPx1, resulting in decreased levels of ROS in BMMSCs and protection of the mitochondrial from oxidative injury. Additionally, irisin was found to up-regulate the expression of SIRT3, an upstream factor that regulates a variety of antioxidant enzymes [ 39 ]. Consistent with our findings, irisin has been documented to provide protection against SIRT3 down-regulation caused by oxidative stress [ 40 ].…”

Section: Discussionmentioning

confidence: 99%

Irisin-loaded electrospun core-shell nanofibers as calvarial periosteum accelerate vascularized bone regeneration by activating the mitochondrial SIRT3 pathway

Hua,

Hou,

Deng

et al. 2023

Regenerative Biomaterials

2

0

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The scarcity of native periosteum poses a significant clinical barrier in the repair of critical-sized bone defects. The challenge of enhancing regenerative potential in bone healing is further compounded by oxidative stress at the fracture site. However, the introduction of artificial periosteum has demonstrated its ability to promote bone regeneration through the provision of appropriate mechanical support and controlled release of pro-osteogenic factors. In this study, a polylactic acid (PLLA)/hyaluronic acid (HA)-based nanofibrous membrane was fabricated using the coaxial electrospinning technique. The incorporation of irisin into the core-shell structure of PLLA/HA nanofibers (PLLA/HA@Irisin) achieved its sustained release. In vitro experiments demonstrated that the PLLA/HA@Irisin membranes exhibited favorable biocompatibility. The osteogenic differentiation of bone marrow mesenchymal stem cells (BMMSCs) was improved by PLLA/HA@Irisin, as evidenced by a significant increase in alkaline phosphatase (ALP) activity and matrix mineralization. Mechanistically, PLLA/HA@Irisin significantly enhanced the mitochondrial function of BMMSCs via the activation of the sirtuin 3 antioxidant pathway. To assess the therapeutic effectiveness, PLLA/HA@Irisin membranes were implanted in situ into critical-sized calvarial defects in rats. The results at four and eight weeks post-surgery indicated that the implantation of PLLA/HA@Irisin exhibited superior efficacy in promoting vascularized bone formation, as demonstrated by the enhancement of bone matrix synthesis and the development of new blood vessels. The results of our study indicate that the electrospun PLLA/HA@Irisin nanofibers possess characteristics of a biomimetic periosteum, showing potential for effectively treating critical-sized bone defects by improving the mitochondrial function and maintaining redox homeostasis of BMMSCs.

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“…It was demonstrated that topical irisin treatment reduced alveolar bone loss and oxidative stress while increasing Sirt3 expression in periodontal tissues in experimentally induced rat models of diabetes and periodontitis. By culturing periodontal ligament cells (PDLCs) in vitro, it was found that irisin could partially restore suppressed cell viability, reduce intracellular oxidative stress and mitochondrial dysfunction, and restore impaired osteogenic and osteoclastogenic abilities in PDLCs upon exposure to high glucose and proinflammatory stimulation [ 124 ]. However, caution should be exercised in the use of a strategy to increase SIRT3 expression, ensuring tissue specificity to avoid exacerbating pathological effects.…”

Section: Possibilities For Gene Therapy Based On Recombinant Adeno-as...mentioning

confidence: 99%

Eternal Youth: A Comprehensive Exploration of Gene, Cellular, and Pharmacological Anti-Aging Strategies

Kitaeva,

Solovyeva,

Blatt

et al. 2024

IJMS

4

0

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The improvement of human living conditions has led to an increase in average life expectancy, creating a new social and medical problem—aging, which diminishes the overall quality of human life. The aging process of the body begins with the activation of effector signaling pathways of aging in cells, resulting in the loss of their normal functions and deleterious effects on the microenvironment. This, in turn, leads to chronic inflammation and similar transformations in neighboring cells. The cumulative retention of these senescent cells over a prolonged period results in the deterioration of tissues and organs, ultimately leading to a reduced quality of life and an elevated risk of mortality. Among the most promising methods for addressing aging and age-related illnesses are pharmacological, genetic, and cellular therapies. Elevating the activity of aging-suppressing genes, employing specific groups of native and genetically modified cells, and utilizing senolytic medications may offer the potential to delay aging and age-related ailments over the long term. This review explores strategies and advancements in the field of anti-aging therapies currently under investigation, with a particular emphasis on gene therapy involving adeno-associated vectors and cell-based therapeutic approaches.

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Knockdown of SIRT3 perturbs protective effects of irisin against bone loss in diabetes and periodontitis

Cited by 10 publications

References 75 publications

Irisin-loaded electrospun core-shell nanofibers as calvarial periosteum accelerate vascularized bone regeneration by activating the mitochondrial SIRT3 pathway

Irisin-loaded electrospun core-shell nanofibers as calvarial periosteum accelerate vascularized bone regeneration by activating the mitochondrial SIRT3 pathway

Irisin-loaded electrospun core-shell nanofibers as calvarial periosteum accelerate vascularized bone regeneration by activating the mitochondrial SIRT3 pathway

Eternal Youth: A Comprehensive Exploration of Gene, Cellular, and Pharmacological Anti-Aging Strategies

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