Roles of Cell Cyle Regulators Cyclin D1, CDK4, and p53 in Knee Osteoarthritis

Zhu, Xiongbai; Yang, Shengwu; Lin, Wenjun; Wang, Lu; Ying, Jinwei; Ding, Yewei; Chen, Xin

doi:10.1089/gtmb.2016.0020

Cited by 31 publications

(27 citation statements)

References 26 publications

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“…As a function of the DNA damage magnitude, p53 may orchestrate homeostatic activities or dysfunctional responses, such as irreversible cell cycle arrest, senescence, or apoptosis [ 27 ] ( Figure 1 ). A recent report explored the correlation of gene and protein expression of cyclin D1, cyclin-dependent kinase 4, and p53 in cartilage derived from a large cohort of patients and healthy controls and showed that cyclin D1 and cyclin-dependent kinase 4 are negatively correlated with the disease grade in knee OA, in agreement with increased p53 [ 28 ].…”

Section: Oa In the Context Of Aging And Metabolic Deregulationmentioning

confidence: 99%

Emerging Players at the Intersection of Chondrocyte Loss of Maturational Arrest, Oxidative Stress, Senescence and Low‐Grade Inflammation in Osteoarthritis

Minguzzi

Cetrullo

D’Adamo

et al. 2018

Oxidative Medicine and Cellular Longevity

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The prevalence of Osteoarthritis (OA) is increasing because of the progressive aging and unhealthy lifestyle. These risk factors trigger OA by removing constraints that keep the tightly regulated low turnover of the extracellular matrix (ECM) of articular cartilage, the correct chondrocyte phenotype, and the functionality of major homeostatic mechanisms, such as mitophagy, that allows for the clearance of dysfunctional mitochondria, preventing increased production of reactive oxygen species, oxidative stress, and senescence. After OA onset, the presence of ECM degradation products is perceived as a “danger” signal by the chondrocytes and the synovial macrophages that release alarmins with autocrine/paracrine effects on the same cells. Alarmins trigger innate immunity in the joint, with important systemic crosstalks that explain the beneficial effects of dietary interventions and improved lifestyle. Alarmins also boost low-grade inflammation: the release of inflammatory molecules and chemokines sustained by continuous triggering of NF-κB within an altered cellular setting that allows its higher transcriptional activity. Chemokines exert pleiotropic functions in OA, including the recruitment of inflammatory cells and the induction of ECM remodeling. Some chemokines have been successfully targeted to attenuate structural damage or pain in OA animal models. This represents a promising strategy for the future management of human OA.

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Section: Oa In the Context Of Aging And Metabolic Deregulationmentioning

confidence: 99%

Emerging Players at the Intersection of Chondrocyte Loss of Maturational Arrest, Oxidative Stress, Senescence and Low‐Grade Inflammation in Osteoarthritis

Minguzzi

Cetrullo

D’Adamo

et al. 2018

Oxidative Medicine and Cellular Longevity

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“…Phosphorylation of pRB leads to the release of E2F from pRB binding allowing DNA transcription and cell proliferation to take place, driving the cell cycle from G1 phase into S phase [Tobin et al, ]. A study suggested that cyclin Dl expression is associated with knee osteoarthritis (KOA) [Zhu et al, ]. Besides this study, there is not a lot of current research that investigates the role of cyclin proteins and their relation to the development of OA.…”

mentioning

confidence: 99%

Retracted: Cyclin D1 Gene Silencing Promotes IL‐1β‐Induced Apoptosis in Rat Chondrocytes

Zan

Yao

et al. 2017

J of Cellular Biochemistry

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This study investigated the effects of cyclin D1 gene silencing on cell proliferation and apoptosis of interleukin-1b (IL-1b)-induced osteoarthritis (OA) chondrocytes. Chondrocytes from healthy sprague-dawley rats were divided into blank, OA model (chondrocytes underwent IL-1b inducement), OA trial (chondrocytes underwent IL-1b inducement with cyclin D1-shRNA treatment), and negative control (NC; chondrocytes underwent IL-1b inducement and control-shRNA treatment) groups. Cell proliferation was assessed by CCK-8 assay, and cell cycle and apoptosis by flow cytometry. qRT-PCR and Western blotting were performed to detect cyclin D1 and apoptosisrelated factors expression levels. Chondrocyte proliferation increased after 72-96 h after incubation. The OA trial group exhibited reduced cell proliferation at 48, 72, and 96 h after treatment. The OA model, OA trial, and NC groups all contained more cells arrested in G1 phase and had higher apoptosis rates than the blank group. Additionally, the OA trial group contained more cells arrested in G1 phase, with increased apoptosis rates compared to the OA model and NC groups. The OA model group had lowest expression of cyclin D1 whereas the blank group contained the highest among the four groups. qRT-PCR also showed that the OA model, OA trial, and NC groups all had increased expression levels of Bax and reduced expression levels of Bcl-2 and P53 compared to the blank group, whereby by the OA group had the most significant change. The combined evidence in our study shows that cyclin D1 gene silencing suppresses proliferation and induces apoptosis of rat chondrocytes in IL-1b-induced OA.

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“…MiR-204-5p overexpression has been found to induce downregulation of CCND1 , resulting in differentiation of human MSCs toward adipogenic rather than osteogenic lineage [ 45 ]. Zhu et al also found grade-dependent decrease in mRNA and protein expressions of CCND1 among the knee OA population, compared to healthy controls [ 46 ]. These findings supported our results regarding miR-204-5p regulation in aging bone process, where up-regulated miR-204-5p was postulated to down-regulate SOX11 and be involved in the cell cycle arrest of osteoblasts, leading to clinical observations of increased bone loss among the geriatric population.…”

Section: Discussionmentioning

confidence: 99%

Identification of novel genes in aging osteoblasts using next-generation sequencing and bioinformatics

et al. 2017

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During the aging process, impaired osteoblastic function is one key factor of imbalanced bone formation and age-related bone loss. The aim of this study is to explore the differentially expressed genes in normal and aged osteoblasts and to identify genes potentially involved in age-related alteration in bone physiology. Based on next generation sequencing and bioinformatics analysis, 12 differentially expressed microRNAs and 22 differentially expressed genes were identified. Up-regulation of miR-204-5p was validated in an array of osteoporotic hip fracture in the Gene Expression Omnibus database (GSE74209). The putative targets for miR-204-5p were Kruppel-like factor 7 (KLF7) and SRY-box 11 (SOX11). Ingenuity Pathway Analysis identified SOX11, involved in osteoarthritis pathway and differentiation of osteoblasts, together with miR-204-5p, a potential upstream regulator, suggesting the critical role of miR-204-5p-SOX11 regulation in the aging process of human bones. In addition, as semaphorin 3A (SEMA3A) and ephrin type-A receptor 5 (EPHA5) were involved in nervous system related biological functions, we postulated a potential linkage between SEMA3A, EPHA5 and development of neurogenic heterotopic ossification. Our findings implicate new candidate genes in the diagnosis of geriatric musculoskeletal disorders, and provide novel insights that may contribute to the elaboration of new biomarkers for neurogenic heterotopic ossification.

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Roles of Cell Cyle Regulators Cyclin D1, CDK4, and p53 in Knee Osteoarthritis

Abstract: Expression of the Cyclin D1, CDK4, and p53 genes are correlated with the disease grades of KOA.

Cited by 31 publications

References 26 publications

Emerging Players at the Intersection of Chondrocyte Loss of Maturational Arrest, Oxidative Stress, Senescence and Low‐Grade Inflammation in Osteoarthritis

Emerging Players at the Intersection of Chondrocyte Loss of Maturational Arrest, Oxidative Stress, Senescence and Low‐Grade Inflammation in Osteoarthritis

Retracted: Cyclin D1 Gene Silencing Promotes IL‐1β‐Induced Apoptosis in Rat Chondrocytes

Identification of novel genes in aging osteoblasts using next-generation sequencing and bioinformatics

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