Osteoarthritis senescence Dendrobine (DEN) is reported to inhibit inflammation and oxidative stress in some diseases, but its role in chondrocyte senescence and OA progress has not yet been elucidated. Chronic accumulation of senescent cells is associated with age-related disease, including osteoarthritis, a Senescence in osteoarthritis: from mechanism to potential treatment Yikai Liu, Zian Zhang, Tao Li, Hao Xu and Haining Zhang* Abstract Osteoarthritis (OA) is an age-related cartilage degenerative disease, and chondrocyte senescence has been exten-sively studied in recent years. However, whether physical exercise is beneficial for preventing the progression of OA symptoms with Ageing and excessive mechanical strain on the articular cartilage have both been associated with the development of knee osteoarthritis (OA). Increased numbers of senescent chondrocytes are found in OA cartilage. However, its protective effects against OA have not been elucidated. Clearance of these senescent cells using senolytics resulted in the increased functionality of the remaining chondrocytes with rejuvenation of cartilage soon after (Jeon et al. Though it contributes to aged-related pathologies, cellular senescence also plays beneficial roles during development and wound healing in the regulation of Background Osteoarthritis (OA) is a degenerative joint disease associated with aging, which often leads to joint stiffness and disability. Heterogeneous nuclear ribonucleoprotein D (HNRNPD) is an RNA Keywords: osteoarthritis, aging, senescence, cartilage, cells. We focus on the underlying It is thought that cellular senescence may play a significant role in the pathology of OA, with chondrocytes exhibiting a variety of senescence-associated phenotypes. The results showed that senescence-related-β-galactosidase, p53, p21 and Beclin-1 were found to be increased, but Lamin B1 was found to Osteoarthritis (OA) is an autoimmune disease associated with increasing age. g. An increasing number of studies have suggested that the accumulation of senescent cells triggering by various stresses in the local joint contributes to the Background: Chondrocyte senescence and inflammation are hallmarks of osteoarthritis (OA). In the last years, the research community has focused on understanding the molecular mechanisms that led to the pathogenesis of the disease, trying to identify different molecular and clinical phenotypes along with the discovery of new therapeutic opportunities. J Clin Invest. Different types of cell-to-cell Keywords: cellular senescence, epigenetics, osteoarthritis. In osteoarthritis, senescent chondrocytes contribute to cartilage degradation possibly via MMP activity. The recent literature was reviewed to find studies providing new insights into the connection between aging and OA. Cellular senescence is considered to be a fundamental pathogenic mechanism in the development of OA and has attracted increasing attention. Existing research has shed light Osteoarthritis (OA) is strongly linked to aging but the mechanisms for this link are incompletely understood. , 2017; McGonagle et al. Natural killer (NK) cells participate in the elimination of senescent cells in multiple organs. Here, the authors show that GATD3A deficiency induces fibroblast-like Sometimes referred to as the senescent secretory phenotype 8, 18, this form of cell senescence may be particularly relevant to the development of osteoarthritis. Piezo1, a mechanosensitive Ca 2+ channel, Underlying mechanisms affecting osteoarthritis. • Therapeutics to mitigate senescence in osteoarthritis include senolytic and senomorphic approaches. Cartilage degeneration in OA involves a senescent Increasing evidence supports the notion that oxidative stress and cellular senescence play a crucial role in the onset and advancement of osteoarthritis (OA) [2], [3], [4]. With aging, its prevalence keeps increasing. OA is primarily caused by trauma induced by an external force or by age-related cartilage damage. For decades, osteoarthritis (OA) has been regarded as a pathological Osteoarthritis (OA), the most common form of arthritis, is a disease of the synovial joints that is characterized by Senescent cells accumulate as an organism ages, result- The recent publication in the Annals of Rheumatic Diseases by Zhang et al 1 “Mechanical overloading promotes chondrocyte senescence and osteoarthritis development through downregulating FBXW7” includes conclusions that “Inhibition of JNK activity ameliorated chondrocyte senescence and cartilage degeneration” and “This study suggests that targeting AT-III could alleviate osteoarthritis by inhibiting chondrocyte senescence through NF-κB pathway, which indicated that AT-III is a prospective drug for osteoarthritis treatment. Objective: Osteoarthritis (OA) is the most common degenerative joint disease leading to disability worldwide. OA, osteoarthritis; DMOADs, disease modifying anti-osteoarthritis drugs; STACs, sirtuin-activating compounds; NSAIDs, non-steroidal anti-inflammatory drugs; SnCs, Senescent cell population with ZEB1 transcription factor as its main regulator promotes osteoarthritis in cartilage and meniscus Ann Rheum Dis , 82 ( 3 ) ( 2023 ) , pp. 5 , 17602 (2015). 1. D. , 2008). Senescent cells remain viable, but show alterations in phenotype, e. As IL-1β induces dedifferentiation of chondrocytes, SOX9 and Col II are downregulated through α-, β-, and γ-catenin in the Wnt signaling pathway 79 . 2024 Jun 4;13(11):976. Here, the authors show that GATD3A deficiency induces fibroblast-like synoviocyte senescence in mice and demonstrate that targeting GATD3A alleviates symptoms in mouse models of osteoarthritis. 2018;128(4):1229–1237. Aging and mechanical overload are prominent risk factors for osteoarthritis (OA), which lead to an imbalance in redox homeostasis. The The musculoskeletal system supports the movement of the entire body and provides blood production while acting as an endocrine organ. Starting at Accumulation of senescent cells is the prominent risk factor for osteoarthritis (OA), accelerating the progression of OA through a senescence-associated secretory phenotype Due to the complexity and heterogeneity of osteoarthritis pathogenesis, the combined removal of local senescent cells and the transplantation of MSCs may be a good therapeutic option to date 33,43 Background: Cellular senescence is associated with age-related pathological changes, senescent cells promote the development of knee osteoarthritis. Possible mechanisms for organismal aging include loss of heterochromatin1, free radicals, pro- grammed senescence, telomere Cellular senescence has been implicated in multiple musculoskeletal diseases, including OA and osteoporosis []. Senescent chondrocytes have the ability to demonstrate the senescence-associated secretory phenotype (SASP) and release substances that might cause alterations in osteoarthritic tissues. Cellular senescence, the loss of the ability of cells to divide, has Osteoarthritis (OA) poses a significant challenge in orthopedics. 3a), which has been suggested to have a potential role in regulating mitochondrial function28. We first assessed the expression patterns of SIRT families in cartilage tissues from OA patients and controls (Fig. Introduction. Purpose: Cellular senescence has been identified as a major factor in the pathogenesis of osteoarthritis (OA). Chondrocyte Osteoarthritis (OA) is the most common age-related and post-traumatic degenerative joint disease. SASP factors secreted by senescent chondrocytes primarily include inflammatory factors and MMP degrading enzymes [45], which trigger excessive degradation of chondrocyte ECM. Osteoarthritis; Senescence; Abstract. The development of osteoarthritis (OA) correlates with a rise in the number of senescent cells in joint tissues, and the senescence-associated secretory phenotype (SASP) Osteoarthritis; Senescence; Translational research; Abstract. Osteoarthritis Cartilage 17 , 971–979 (2009). Osteoarthritis (OA) pathology overlaps with the senescence of cells in joint tissue and the senescence-associated secretory phenotype. Infrapatellar fat pad (IPFP) is closely associated with the development and progression of knee osteoarthritis (OA), but the underlying mechanism remains unclear. METHODS: Knees of male SAMP8 and SAM-resistant 1 (SAMR1) mice as The clearance of local senescent cells and the implantation of hMSCs to the joint have provided a therapeutic paradigm for osteoarthritis (Jeon et al. The progression of OA is marked by the loss of articular cartilage, joint remodeling, and changes in the synovial membrane Osteoarthritis (OA) is one of the most common degenerative joint diseases among elderly individuals, which is primarily characterized by cartilage destruction, synovial Chondrocyte senescence is an important mechanism underlying the development of osteoarthritis, resulting in reduced production of extracellular matrix proteins and an increase in the release of proinflammatory factors [ 3– 5]. And it is only in the last decade or so that cellular senescence has gradually become cross-linked with osteoarthritis. Considering that both Sirt1 and Sirt6 were reduced in cartilage tissues Abstract. , 2016). As aging is a significant risk factor for OA, there is a growing urgency to develop specific therapies that target the underlying mechanisms of aging associated with this condition. Osteoarthritis (OA) is a chronic and debilitating condition that affects more than 30 million individuals in the United States . However, regulatory mechanisms underlying chondrocyte senescence in OA remain unclear. Stem cell–homing hydrogel-based miR-29b-5p delivery promotes cartilage regeneration by suppressing senescence in an osteoarthritis rat model. Inflammatory pathways are regarded as central mechanisms in the onset and progression of OA. Furthermore, we examined the type of cells Chondrocyte senescence and inflammation are hallmarks of osteoarthritis (OA). Key words: aging, articular cartilage, chondrocyte, mitochondria, osteoarthritis, oxidative damage, senescence, telomere Abstract The incidence of osteoarthritis (OA), the disease characterized by joint pain and loss of joint form and function due to articular cartilage degeneration, is directly correlated with age. Natural killer (NK) Accumulating data demonstrate a clear relationship between the senescence of articular chondrocytes and OA formation and progression. As one of the hallmarks of ageing, increased senescent cell burden in various tissues is a major contributor to ageing and age-related disease. However, most commonly used senescence markers, including p16, p21 and senescence-associated β galactosidase (SA-βgal), are intracellular, In a mouse model of post-traumatic osteoarthritis (OA), local clearance of senescent cells using senolytic compound UBX0101 has been shown to mitigate the development of post-traumatic OA and promote a pro-regenerative environment (Jeon et al. Here, we identified a critical role for Yes-associated protein (YAP), a major Keywords: osteoarthritis, cell senescence, aging, cytokines, therapeutics. However, there is no comprehensive bibliometric analysis in this field. Although there are multiple joint tissues and cell types involved in OA pathology, chondrocytes have been the focus of the vast majority of studies to date that address a role for Osteoarthritis (OA) is the most common joint disease. (a) Mitochondrial anion superoxide (O 2 −) production under basal and menadione conditions was evaluated by the fluorescence intensity of MitoSox ®. Senescent chondrocytes (SnCs) are found in OA cartilage, and the clearance of those chondrocytes prevents OA progression. Nearly 250 million people suffer from OA, making it a leading cause of disability in the elderly population []. Cell hypertrophy generally refers to an increase in cell size and volume. This study aims to identify OA-specific microRNAs (miRNAs) targeting chondrocyte senescence to alleviate OA progression. Chondrocyte hypertrophy or chondrocyte senescence is thought to play a role in the initiatio Chondrocyte senescence is a key driver of osteoarthritis (OA). Typically, chondrocyte senescence is believed to serve an important role in the development and progression of OA. gerates chondrocyte senescence and osteoarthritis progression, whereas intra-articular injection of adenovirus-Sirt6 markedly attenuates surgical destabilization of medial meniscus-induced Cell senescence was determined by senescence-associated β-galactosidase (SA-β-Gal) assay after FAP overexpressing or knockdown in chondrocytes. While exist-ing rheumatologic therapies have been disappointing to date, research is ongo-ing regarding finding new or repurpos-ing existing medications for mitigating senescence in osteoarthritis. To identify the potential driver of senescence in OA, we surveyed the publicly available scRNA-seq GEO data set GSE176308. As the main cell type of the synovium, the senescence of FLS plays a crucial role in the pathological progression of OA [10]. Heterogeneous nuclear ribonucleoprotein D (HNRNPD) is an RNA-binding protein whose expression imbalance is associated with cell senescence, but the role of HNRNPD in the occurrence and development of OA has not been Nature Reviews Rheumatology - Controlling chondrocyte senescence. Manuscripts most relevant to aging and OA that examined one or more of the hallmarks of aging were selected Osteoarthritis (OA) is an age-related cartilage degenerative disease, and chondrocyte senescence has been extensively studied in recent years. Senescent cells cease dividing and release senescence-associated secretory proteins (SASPs), which may cause inflammation and cause other cells to Schematic image of (a) endochondral ossification in the embryonic cartilage and (b) progression of osteoarthritis in the articular cartilage. Introduction Osteoarthritis (OA) Osteoarthritis (OA) is the most prevalent disease of synovial joints (around 4. Table 1. Removal of senescent chondrocytes decelerates the process of osteoarthritis in surgery-induced osteoarthritis mice . [] Instead, it is switched to senescent Osteoarthritis (OA) is a common degenerative joint disease, particularly prevalent among the elderly, and it significantly contributes to mobility limitations and decreased quality of life in this Osteoarthritis (OA) is an age-related disease characterised by the accumulation of senescent chondrocytes, which drives its pathogenesis and progression. Osteoarthritis (OA) has surpassed diabetes and cardiovascular diseases, and become the most common chronic disease and the leading cause of morbidity. , 2007, Steffen et al. The accumulation of senescent chondrocytes in aging human cartilage contributes to the high incidence of OA. To investigate the role of the NHE during OA under mechanical Cellular senescence is a major characteristic of aging and contributes to many diseases, such as the progression of OA [13]. Conclusion: This work suggests that mitochondria from OA patients could be involved Background: Animal models of spontaneous osteoarthritis (OA) are sparse and not well characterized. PubMed PMID: 29608139. As an age-related disease, its incidence rate increases with the Briefly, 12 mice were used to conduct the HE, Saf O and IHC staining to explore the association between facet joint osteoarthritis and chondrocyte senescence (2 groups: Control and Standing mice group, 6 mice per group), and 18 mice were used to determine the experiments of HE, Saf O, IHC staining and X-ray microscope scanning to explore the GATD3A was significantly decreased in OA-FLSs (Fig. Multiple mechanisms have been demonstrated and these include cellular senescence, telomere attrition, mitochondrial dysfunction, stem cell exhaustion, genomic instability, altered intercellular communication, epigenetic alterations, loss of proteostasis, and deregulated Introduction Osteoarthritis (OA) Osteoarthritis (OA) is the most prevalent disease of synovial joints (around 4. Downregulation of Sirt6 is associated with chondrocyte senescence and OA a Representative radiographic images and gross appearance of the cartilage of OA patients and controls, H&E, Safranin O Mitochondrial Role on Cellular Apoptosis, Autophagy, and Senescence during Osteoarthritis Pathogenesis Cells. We classified the cluster of cells into Early OA nonpainful, Early_OA painful, and Endstage_OA painful (Figure 1 A, left panel). Hypertrophic differentiation of chondrocytes can also be characterized by the high expression of collagen type X, runt-related transcription factor 2 (RUNX2), and MMP13. [] During OA development, the healthy phenotype of chondrocytes that maintains the cartilage matrix metabolic homeostasis is lost gradually. In osteoporosis, the senescence-associated secretory phenotype (SASP) from Underlying mechanisms affecting osteoarthritis. Despite its therapeutic potential, the exact molecular mechanisms underlying LSF's action in OA have remained enigmatic. Recent studies emphasized the existence of senescent synoviocytes in OA and the therapeutic effect of removing senescen A ging is a crucial driving force in human degenerative disorders. To address this Senescence in osteoarthritis: from mechanism to potential treatment. Sci. Several hallmarks of senescence are associated The contribution of the hallmarks of aging to cellular senescence and the development of osteoarthritis (OA). Chondrocyte senescence and reduced lubrication play pivotal roles in the pathogenesis of age-related osteoarthritis (OA). Osteoarthritis (OA) is a common degenerative joint disorder observed in the field of orthopedics. Dendrobine (DEN) is reported to inhibit Ageing is the most common pathogenesis of OA. Authors Andrea Dalmao However, the percentage of senescent cells was higher in OA than N cybrids. Mechanistically, Sirt6 can directly interact with STAT5 and deacetylate STAT5, thus inhibiting the IL Targeting senescence for OA therapy is a promising new approach that deserves further investigation and may enhance the effectiveness of existing therapeutics and provide relief for patients with OA. However, an effective and noninvasive approach to OA Osteoarthritis (OA) is a prevalent disease among elderly people and is often characterized by chronic joint pain and dysfunction. Exercise is one of the most important non-pharmacological treatments and is prescribed as an indispensable treatment for OA. An OA model with chondrocyte-specific FAP knockout mice was applied to investigate the role of FAP in chondrocyte senescence and OA development. Here, we provide strong in vivo evidence that osteoarthritic mice that received gene therapy (using lentiviruses encoding DR8-WT or DR8 The mechanisms underlying fibroblast-like synoviocyte senescence and its impact on osteoarthritis progression are unclear. Senescent cells exhibit distinct features, including mitochondrial dysfunction and the excessive accumulation and release of reactive oxygen species (ROS), which are highly correlated and lead to a vicious cycle of Osteoarthritis (OA) is an autoimmune disease associated with increasing age. F. Keywords: osteoarthritis, nitidine chloride, ROS, senescence, NLRP3 inflammasome, MAPK, NF-κB Citation: Lin C, Ge L, Tang L, He Y, Moqbel SAA, Xu K, Ma D, Zhou X, Cellular senescence denotes a stable, irreversible condition wherein cells undergo growth arrest while maintaining metabolic activity [5]. Aging is one of the Cellular senescence is a driver of various aging-associated disorders, including osteoarthritis. in 1961 as limited replicative potential of normal cultured human fibroblasts, 7,8 was thought to be an in vitro phenomenon. Osteoarthritis (OA) is one of the most common chronic musculoskeletal disorder worldwide, representing a major source of disability, pain and socioeconomic burden. However, targeting SnCs is challenging due to the absence of a senescent chondrocyte-specific marker. Osteoarthritis is a morbid and costly condition affecting an increasingly larger segment of the population with a lack of effective treatment options. Osteoarthritis (OA) is a degenerative joint disease characterized by low-grade inflammation and cartilage degradation. Age-related accumulation of senescent cells in articular cartilage, subchondral bone, synovial membrane, and sub-patellar fat pads Chondrocyte PDZK1 is a potential candidate during chondrocyte senescence and OA progression in response to mechanical overload. Mitochondrial dysfunction and oxidative stress can induce chondrocyte senescence. The main pathological features of OA are the degeneration of Cellular senescence is associated with aging and age-related chronic diseases such as diabetes, cardiovascular disease, muscle decline, Alzheimer’s, and osteoarthritis (OA) (1–4). 1a), and the results demonstrated that Sirt1 and Sirt6 were significantly downregulated (Fig. Osteoarthritis (OA) is the most common joint disease. Background Animal models of spontaneous osteoarthritis (OA) are sparse and not well characterized. Key words osteoarthritis, senescence, DNA damage, pro-inflammatory cytokines, epigenetic modifications Cite this article: Lawson MG, Ritchison HM: Molecular basis of senescence in osteoarthritis. Aging is a critical factor for different age-related diseases. Here we show that clathrin-mediated endocytosis and The prevalence of osteoarthritis (OA) rises directly with age and it is the most common cause of chronic disability in older adults 1, 2. The increasing incidence of osteoarthritis (OA) with age, coupled with the lack of effective non-surgical treatments to mitigate disease progression, make OA one of the most common causes of chronic pain and disability in Osteoarthritis (OA) is the most common joint disease. 1136/ard-2022-223227 The peer-reviewed English language literature was searched on PubMed using keywords including senescence, aging, cartilage, and osteoarthritis, for original studies and reviews published from 1993 to 2023 with a major focus on more recent studies. A The pathophysiology of osteoarthritis is poorly understood; cell senescence is deemed to be contributory. Induction of dysfunction, senescence, and death in chondrocytes, which are essential for cartilage formation and functionality by maintaining the Osteoarthritis (OA) is a common degenerative joint disease that disproportionately impacts the elderly population on a global scale. It is characterized by cartilage degeneration, abnormal bone Senescence in osteoarthritis pathology. The senescence pathway has many beneficial effects and is seen to be activated in damaged/stressed cells, as well as during embryonic development and wound healing. However, there is limited research on the mechanisms underlying fibroblast-like synoviocyte Senescent cells can secrete senescence-associated secretory phenotype (SASP) factors, such as inflammatory cytokines and growth factors [44]. PMCID: PMC5873863 Unity Biotechnology, Buck Osteoarthritis (OA) has been recognized as an age-related degenerative disease commonly seen in the elderly that affects the whole “organ” including cartilage, subchondral bone, synovium, and muscles. et al. Accumulating evidence points to chondrocyte senescence as a key driver in OA development. Growing evidence suggests that senescence acts as a mediator in inflammation-induced OA. Cellular senescence is characterized by cell cycle arrest and increasing senescence-associated secretory proteins. Methods Senescent cells (SnCs) are implicated in the pathogenesis of age-related diseases including osteoarthritis (OA), in part via expression of a senescence-associated secretory phenotype (SASP) that includes immunologically relevant factors and cytokines. This Here we show that Sirt6 deficiency exaggerates chondrocyte senescence and osteoarthritis progression, whereas intra-articular injection of adenovirus-Sirt6 markedly attenuates surgical destabilization of medial meniscus-induced osteoarthritis. The purpose of the present study is to examine OA-related changes and mechanisms in senescence-accelerated mouse prone 8 (SAMP8) that displays a phenotype of accelerated aging. (c) Relative mRNA expression levels in the presence of menadione (50 µM), nuclear factor erythroid 2-like As the unique cell type in articular cartilage, chondrocyte senescence is a crucial cellular event contributing to osteoarthritis development. The aim of this study is Lei's formula (LSF), a traditional Chinese herbal remedy, is recognized for its remarkable clinical effectiveness in treating osteoarthritis (OA). However, the persistence and accumulation of senescent cells in Cellular senescence is the inability of cells to proliferate, which has both beneficial and detrimental effects on tissue development and homeostasis. The nucleolus is the most prominent subnuclear structure involved in rRNA synthesis and protein translation in cells and is thus linked to the regulation of cell homeostasis and senescence (Grummt, 2013, Guarente, 1997, Hansen et al. Here, we identified a critical role for Yes-associated protein (YAP), a major effector of Hippo signaling, in maintaining a younger state of human mesenchymal stem cells (hMSCs) and ameliorating osteoarthritis in mice. Chondrocyte senescence is the essential pathogenic mechanism that can both promote the progression of age-associated osteoarthritis (OA) and post-traumatic OA (PTOA). Rep. Senescent chondrocytes, senescent mesenchymal stem cells, and osteoarthritis chondrocytes can upregulate the expression of chondro-degrading enzymes by releasing pro-inflammatory cytokines (SASPs), thereby causing cartilage metabolism imbalance. Here, it is find that IPFP from OA patients can secret small extracellular vesicles (sEVs) and deliver them into articular chondrocytes. Recent studies have elucidated the important role of cellular senescence in the development of OA [6]. In addition to articular cartilage degradation, cellular senescence, synovial inflammation, and epigenetic alterations may all have a Aging and Cellular Senescence. 1b). Osteoarthritis (OA) is the most common joint disease that causes pain and disability in the adult population. Discover the Schematic representation of age-related stress-induced senescence in articular chondrocytes and the effect of SASP on osteoarthritis. Senescence of joint tissues particularly ch The development of osteoarthritis (OA) correlates with a rise in the number of senescent cells in joint tissues, and the senescence-associated secretory phenotype (SASP) has been implicated in cartilage degradation and OA. IL-1β is also associated with the induction of NO synthase, which has the ability to activate JNK, and JNK is a well-known inducer of senescence and mediator of osteoarthritis 78. These substances include The role of cellular senescence in Osteoarthritis. Accumulation of SCs in the joint tissue increases with age and often promotes cartilage damage that plays chondrocyte senescence. In the last years, the research community has focused on understanding the molecular mechanisms that led to the pathogenesis of the disease, trying to identify different molecular and clinical phenotypes along with the discovery of new therapeuti The mechanisms underlying fibroblast-like synoviocyte senescence and its impact on osteoarthritis progression are unclear. (b) Data expressed as the ratio of basal/menadione O 2 − between N and OA. 3390/cells13110976. In addition, senescent mesenchymal stem Osteoarthritis is a common degenerative disease characterized by senescence of chondrocytes [46], [47], however, the role and mechanisms of ASIC1a in osteoarthritis chondrocyte senescence remain unclear. Methods Knees of male SAMP8 and SAM-resistant 1 (SAMR1) mice as 1 Introduction. Age-related mitochondrial Cellular senescence is a state of stable proliferation arrest of cells. Osteoarthritis (OA) is an age-related disorder that is strongly associated with chondrocyte senescence. A better Mechanisms and therapeutic implications of cellular senescence in osteoarthritis Article 18 November 2020. Recently, growing evidence of chondrocyte senescence in the pathogenesis of OA has been found, and targeting senescence has started to be recognized as a therapeutic approach for OA. The chronic rise of senescent cells has a close correlation with age-related diseases such as OA, and the senescence-associated secretory phenoty Osteoarthritis (OA) is a degenerative joint disease characterized by low-grade inflammation and cartilage degradation. Imbalance between pro-oxidant and anti-oxidant forces, resulting in oxidative stress, has been associated with cellular damage and senescence across different cell types [5]. 1 There are more than 300 million patients with knee osteoarthritis (KOA) and is projected to Osteoarthritis (OA) is a common joint disease characterized by progressive cartilage loss that causes disability worldwide. Osteoarthritis (OA) is the most common type of arthritis and is an age-related joint disease that is particularly prevalent in subjects over 65 years old. doi: 10. Osteoarthritis (OA) is a chronic degenerative disease characterized mainly by damage to the articular cartilage and abnormal bone remodeling due to various risks, such as trauma, aging, and obesity [1,2,3]. Chondrocyte senescence has recently been proposed as a key pathogenic mechanism in the etiology of osteoarthritis (OA). Cellular senescence of various types within the joint can promote OA pathology including loss of cartilage, synovium inflammation, and subchondral bone remodeling [8], [9]. As a degenerative disease, cellular senescence has been proposed to be involved in OA []. The presen Correlation between the progression of cellular senescence and osteoarthritis. 7% of global population for knee and hip OA alone), afflicting many millions Overexpression of Sirtuin 6 suppresses cellular senescence and NF-κB mediated inflammatory responses in osteoarthritis development. Typically, chondrocyte senescence is believed to serve an important role in the development and progression of Cellular senescence, initially described by Hayflick et al. Forsythiaside A (FTA), a phenylethanol glycoside isolated from air-dried fruits of Forsythia, has been reported to have significant anti-inflammatory and antioxidant properties. The senescent secretory phenotype is characterized by the increased Moreover, when mice were subjected to an acute trauma to model osteoarthritis, senescent cells accumulated in the site of the injury (Kuyinu et al. Cellular senescence, the loss of the ability of cells to divide, has been noted as the major factor contributing to age-related changes in cartilage - It is well accepted that age is an important contributing factor to poor cartilage repair following injury, and to the development of osteoarthritis. Senescent cells and osteoarthritis: a painful connection. Here, we review the latent mechanism of senescence in OA and propose potential therapeutic methods to target OA-related senescence, with an emphasis on immunotherapies. The pathophysiology of osteoarthritis is poorly understood; cell senescence is deemed to be contributory. However, it is important to note that OA is not an inevitable consequence of aging; it is not a simple “wearing out” of the joints; and aging-related changes in the joint can be distinguished from those due to disease. The strong association Replicative senescence occurs when normal somatic cells stop dividing. Cellular senescence is a process associated with age-related accumulation of SCs in tissue, contributing significantly to the progression of diseases such as OA. Adv. Role of menadione in oxidative stress. Increased numbers of senescent osteocytes have been observed in both murine and human models [37,38], and induction of senescence in murine and human osteocytes has been shown to increase RANKL-dependent bone resorption []. Cellular senescence is a stable form of cell cycle arrest exhibited by cells in response to external stimuli and plays a role in a variety of diseases. Osteoarthritis (OA) is the most common form of arthritis. Zhu, J. Inhibition of cell senescence may Cellular senescence is a consequence of aging, which may lead to OA. Cellular senescence Cellular senescence is a driver of various aging-associated disorders, including osteoarthritis. Age is the main risk factor for many chronic degenerative diseases, including OA. One hallmark Contributions of chondrocyte senescence and menopause to the increased incidence of osteoarthritis in older women: Organism: Homo sapiens: Experiment type: Expression profiling by high throughput sequencing: Summary: Osteoarthritis (OA) is a degenerative joint disease and a leading cause of disability worldwide. Osteoarthritis (OA) is the most common degenerative and progressive joint disease, frequently leading to functional disability and chronic pain in the elderly Osteoarthritis (OA) is a degenerative disease that damages the articular cartilage and entire joint tissue []. Cyclin-dependent kinase Loeser, R. GDF15 Secretory Factor Is a Potential Driver of Chondrocyte Senescence and OA. In this Here, we review the latent mechanism of senescence in OA and propose potential therapeutic methods to target OA-related senescence, with an emphasis on immunotherapies. In a model of posttraumatic OA (PTOA), anterior Sirt6 is an essential factor for chondrocyte senescence and OA pathogenesis. 403 - 415 , 10. UBX0101 also interferes with p53 activity, and its mechanism of action involves the inhibition Objective: Osteoarthritis (OA) is the most common degenerative joint disease leading to disability worldwide. In addition, senescent mesenchymal stem cells and OA Cellular senescence is a state of terminal growth arrest associated with the upregulation of different cell cycle inhibitors, mainly p16 and p21, structural and metabolic alterations, chronic DNA Accumulation of senescent cells is the prominent risk factor for osteoarthritis (OA), accelerating the progression of OA through a senescence-associated secretory phenotype (SASP). cellular and molecular pathways that drive senescence in OA and identifying knowledge gaps to guide future research on this pervasive disease. 2017). 8, eabk0011 (2022) Background Due to the unclear pathogenesis of osteoarthritis (OA), effective treatment for this ailment is presently unavailable. Osteoarthritis (OA) causes serious changes in the metabolic and signaling pathways of chondrocytes, including the mitogen-activated protein kinase (MAPK Senescent cells increase in many tissues with age and induce age-related pathologies, including osteoarthritis (OA). , 2017). Furthermore, changes in the chondrocyte phenotype such as cellular senescence have been proposed as new contributors of the OA progression Materials and methods: We intersected osteoarthritis dataset GSE82107 from GEO database and senescence dataset from CellAge database of human senescence-associated genes based on genetic manipulations experiments plus gene expression profilin, and screened out 4 overlapping genes. 7% of global population for knee and hip OA alone), afflicting many millions worldwide with pain and disability Osteoarthritis (OA) is a chronic, debilitating joint disease characterized by progressive destruction of articular cartilage. In Osteoarthritis (OA) is most prevalent in older individuals and exerts a heavy social and economic burden. 1 Introduction. However, the specific mechanisms by which senescence contributes to OA progression are not fully understood. Western blotting and PCR analyses of synovium and Osteoarthritis (OA) is the most common joint disease that causes pain and disability in the adult population. Yet the effective pharmaceutical treatments applied in the clinical works are merely symptomatic management with uncertainty around thei . However, the specific mechanisms underlying chondrocyte senescence have not been fully addressed. Changes that occur within joint tissues during aging In this review, we summarize current evidence for the role of cellular senescence of different cell types in the onset and progression of osteoarthritis. The causal link between disruptive PTEN/Akt signaling and chondrocyte senescence and the Accumulating evidence indicates that cellular senescence is closely associated with osteoarthritis. Aging and osteoarthritis: the role of chondrocyte senescence and aging changes in the cartilage matrix. Nevertheless, the precise molecular mechanisms underlying chondrocyte senescence remain poorly understood. Stress-activated miR-204 governs senescent phenotypes of chondrocytes to promote osteoarthritis development. With aging, the balance of bone homeostasis is disrupted, leading to bone loss and 2. Moreover, mitochondrial dysfunction leads to the accumulation of excessive ROS in and around the Osteoarthritis of the knee has a complicated pathophysiology that is primarily characterized by mechanical overload, an increase in inflammatory mediators, metabolic alterations, apoptosis, and senescence, all of which contribute to the degeneration and failure of synovial joint components [11]. In the present study, highly lubricated and drug-loaded hydrogel microspheres are designed and Abstract — It is well accepted that age is an important contributing factor to poor cartilage repair following injury, and to the development of osteoarthritis. Osteoarthritis (OA) is a common age-related disease that is correlated with a high number of senescent chondrocytes in joint tissues. Senescent cells release numerous pro-inflammatory factors, such as IL-1 and TNF family members, through paracrine signaling [14]. Although cellular senescence and osteoarthritis are both related Due to the complexity and heterogeneity of osteoarthritis pathogenesis, the combined removal of local senescent cells and the transplantation of MSCs may be a good therapeutic option to date 33, 43 – 45. We have TBK1 pharmacological inhibition mitigates osteoarthritis through attenuating inflammation and cellular senescence in chondrocytes Rui Lu , b Yunkun Qu , a Zhenggang Wang , a Zhiyi He , a Shimeng Xu , a Peng Cheng , a Zhengtao Lv , a Hongbo You , a Fengjing Guo , a Anmin Chen , a, ⁎⁎ Jiaming Zhang , c, ⁎⁎⁎ and Shuang Liang a, ⁎ unknown. The emerging DMOAD therapies under active investigation aim to eliminate senescent chondrocytes or use RNA-based approaches to Osteoarthritis (OA) is the most common joint disease worldwide and imposes substantial mental and physical burdens on elderly individuals. Senescence of joint tissues particularly chondrocytes, synoviocytes (fibroblasts), Here, we review the latent mechanism of senescence in OA and propose potential therapeutic methods to target OA-related senescence, with an emphasis on immunotherapies. altered expression of Cellular senescence is characterized by the architectural and functional attrition of organelles.
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