Underlying mechanism of Sirt1 on apoptosis and extracellular matrix degradation of osteoarthritis chondrocytes

He, Dongsheng; Hu, Xiaojian; Yan, Yi‐Qi; Liu, Hui

doi:10.3892/mmr.2017.6659

Cited by 14 publications

(7 citation statements)

References 26 publications

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“…11 ). In accordance with literature 63 , upregulation of OA-associated gene and protein expression in the presented study could be associated with increased ERK1/2 activation. Similar to MAPK/ERK, also the PI3K/Akt signaling pathway was activated via HP stimulation treatment.…”

Section: Discussionsupporting

confidence: 93%

Hydrostatic pressure-generated reactive oxygen species induce osteoarthritic conditions in cartilage pellet cultures

Rieder

Weihs

Weidinger

et al. 2018

Sci Rep

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Osteoarthritis (OA) is one of the most common causes of disability and represents a major socio-economic burden. Despite intensive research, the molecular mechanisms responsible for the initiation and progression of OA remain inconclusive. In recent years experimental findings revealed elevated levels of reactive oxygen species (ROS) as a major factor contributing to the onset and progression of OA. Hence, we designed a hydrostatic pressure bioreactor system that is capable of stimulating cartilage cell cultures with elevated ROS levels. Increased ROS levels in the media did not only lead to an inhibition of glycosaminoglycans and collagen II formation but also to a reduction of already formed glycosaminoglycans and collagen II in chondrogenic mesenchymal stem cell pellet cultures. These effects were associated with the elevated activity of matrix metalloproteinases as well as the increased expression of several inflammatory cytokines. ROS activated different signaling pathways including PI3K/Akt and MAPK/ERK which are known to be involved in OA initiation and progression. Utilizing the presented bioreactor system, an OA in vitro model based on the generation of ROS was developed that enables the further investigation of ROS effects on cartilage degradation but can also be used as a versatile tool for anti-oxidative drug testing.

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Section: Discussionsupporting

confidence: 93%

Hydrostatic pressure-generated reactive oxygen species induce osteoarthritic conditions in cartilage pellet cultures

Rieder

Weihs

Weidinger

et al. 2018

Sci Rep

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show abstract

“…Moreover, the apoptosis rate of NPMSCs decreased after SIRT1 overexpression, which was accompanied by decreased expression of Bax, cleaved caspase-3 and MMP13, and increased expression of TIMP-1 and Bcl-2. According to the findings of He et al ( 30 ), overexpression of SIRT1 reduces chondrocyte apoptosis and ECM degeneration in subjects with osteoarthritis (OA) by increasing Bcl-2 expression and inhibiting Bax expression. Furthermore, in spinal cord injuries, when SIRT1 is upregulated, cleaved caspase-3 expression was reduced, suggesting a negative association between these two proteins ( 31 ).…”

Section: Discussionmentioning

confidence: 99%

Activation of SIRT1 promotes cartilage differentiation and reduces apoptosis of nucleus pulposus mesenchymal stem cells via the MCP1/CCR2 axis in subjects with intervertebral disc degeneration

Ying

Bai

et al. 2020

Int J Mol Med

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Intervertebral disc degeneration (Idd) is a condition involving disruption of the bone tissue distribution. Nucleus pulposus mesenchymal stem cells (NPMScs) and Sirtuin 1 (SIRT1) play important roles in bone diseases, therefore the aim of the present study was to evaluate the roles of SIRT1 and NPMScs in Idd. First, NPMScs were harvested from patients with Idd. Then, the NPMScs were treated with a SIRT activator, and monocyte chemoattractant protein 1 (McP1) and chemokine receptor 2 (ccR2) inhibitors. Indices related to NPMSc growth, proliferation, differentiation and apoptosis were measured. Subsequently, Idd rat models were established and were transfected with NPMScs overexpressing SIRT1. NPMSc apoptosis and cartilage differentiation were detected in the rat Idd model. SIRT1 expression was found to be decreased, and the expression of McP1 and ccR2 increased in NPMScs of patients with Idd. The upregulation of SIRT1 and the downregulation of the McP1/ccR2 axis promoted cartilage differentiation and reduced the number of apoptotic NPMScs. Furthermore, McP1 reversed the progression of the cartilage differentiation of NPMScs and the inhibition of NPMSc apoptosis induced by SIRT1 overexpression. Moreover, the transplantation of rat NPMScs overexpressing SIRT1 relieved Idd in rats. Therefore, SIRT1 overexpression improved cartilage differentiation and reduced the apoptosis of NPMScs by inactivating the McP1/ccR2 axis, thus attenuating Idd in rats.

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“…Meanwhile, the elevation of SIRT1 positively affects cartilage genes including collagen 2a, collagen 2b, and aggrecan expression [38]. SIRT 1 up-regulation could also suppress OA chondrocyte apoptosis and ECM degradation through increasing Bcl-2 and decreasing Bax, MMP 1, and MMP 13 expression via the inhibition of p38, JNK, and ERK phosphorylation [86].…”

Section: Effect Of Sirt 1 In Oamentioning

confidence: 99%

The role of sirtuin 1 and its activator, resveratrol in osteoarthritis

Deng

Liu

et al. 2019

Bioscience Reports

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Osteoarthitis (OA) is the most common aging-related joint pathology; the aging process results in changes to joint tissues that ultimately contribute to the development of OA. Articular chondrocytes exhibit an aging-related decline in their proliferative and synthetic capacity. Sirtuin 1 (SIRT 1), a longevity gene related to many diseases associated with aging, is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase and master metabolic regulator. Along with its natural activator resveratrol, SIRT 1 actively participates in the OA pathological progress. SIRT 1 expression in osteoarthritic cartilage decreases in the disease progression of OA; it appears to play a predominantly regulatory role in OA. SIRT 1 can regulate the expression of extracellular matrix (ECM)-related proteins; promote mesenchymal stem cell differentiation; play anti-catabolic, anti-inflammatory, anti-oxidative stress, and anti-apoptosis roles; participate in the autophagic process; and regulate bone homeostasis in OA. Resveratrol can activate SIRT 1 in order to inhibit OA disease progression. In the future, activating SIRT 1 via resveratrol with improved bioavailability may be an appropriate therapeutic approach for OA.

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Underlying mechanism of Sirt1 on apoptosis and extracellular matrix degradation of osteoarthritis chondrocytes

Cited by 14 publications

References 26 publications

Hydrostatic pressure-generated reactive oxygen species induce osteoarthritic conditions in cartilage pellet cultures

Hydrostatic pressure-generated reactive oxygen species induce osteoarthritic conditions in cartilage pellet cultures

Activation of SIRT1 promotes cartilage differentiation and reduces apoptosis of nucleus pulposus mesenchymal stem cells via the MCP1/CCR2 axis in subjects with intervertebral disc degeneration

The role of sirtuin 1 and its activator, resveratrol in osteoarthritis

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