Correlation between senescence‐associated beta‐galactosidase expression in articular cartilage and disease severity of patients with knee osteoarthritis

Gao, Shu‐guang; Zeng, Chao; Li, Liangjun; Luo, Wei; Zhang, Fang‐Jie; Tian, Jing; Chen, Cheng; Tu, Min; Xiong, Yilin; Jiang, Wei; Xu, Mai; Lei, Guanghua

doi:10.1111/1756-185x.12096

Cited by 68 publications

(46 citation statements)

References 29 publications

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“…Chondrocytes can be isolated and cultured from TKA cartilage tissue. While patient variability exists, in our experience and in the literature, a consistent percentage of senescent chondrocytes are present in OA patient-derived chondrocytes (21,46,49,50). We found that treating these chondrocytes with a small-molecule senolytic reduced SnC burden and upregulated expression and deposition of type II collagen and aggrecan, the two primary ECM components of cartilage (22).…”

Section: Sncs In the Kneementioning

confidence: 58%

“…For many years, senescent chondrocytes were noted in cartilage tissue discards from diseased joints after total knee arthroplasty surgery (22,(48)(49)(50). Senescent chondrocytes accumulate with age and are present at higher numbers in human OA cartilage compared with age-matched healthy cartilage (18,21,45,46,(50)(51)(52).…”

Section: Sncs In the Kneementioning

confidence: 99%

“…The localization of senescent chondrocytes near osteoarthritic lesions, but not in intact tissue, further suggests a disease connection (46). The positive correlation between the presence and degree of senescence and disease severity (46,49), however, remains controversial. Ongoing clinical trials will address this important question (53).…”

Section: Sncs In the Kneementioning

confidence: 99%

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Senescent cells and osteoarthritis: a painful connection

Jeon¹,

David²,

Campisi³

et al. 2018

Journal of Clinical Investigation

242

217

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Senescent cells (SnCs) are associated with age-related pathologies. Osteoarthritis is a chronic disease characterized by pain, loss of cartilage, and joint inflammation, and its incidence increases with age. For years, the presence of SnCs in cartilage isolated from patients undergoing total knee artificial implants has been noted, but these cells' relevance to disease was unclear. In this Review, we summarize current knowledge of SnCs in the multiple tissues that constitute the articular joint. New evidence for the causative role of SnCs in the development of posttraumatic and age-related arthritis is reviewed along with the therapeutic benefit of SnC clearance. As part of their senescence-associated secretory phenotype, SnCs secrete cytokines that impact the immune system and its response to joint tissue trauma. We present concepts of the immune response to tissue trauma as well as the interactions with SnCs and the local tissue environment. Finally, we discuss therapeutic implications of targeting SnCs in treating osteoarthritis.

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Section: Sncs In the Kneementioning

confidence: 58%

Section: Sncs In the Kneementioning

confidence: 99%

Section: Sncs In the Kneementioning

confidence: 99%

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Senescent cells and osteoarthritis: a painful connection

Jeon¹,

David²,

Campisi³

et al. 2018

Journal of Clinical Investigation

242

217

View full text Add to dashboard Cite

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“…In knee OA, Gao et al . () demonstrated a correlation between SAβGal expression and disease severity of patients. They investigated the levels of SAβGal expression in normal cartilage compared with OA cartilage of differing severity (mild, moderate, and severe).…”

Section: Senescence In Osteoarthritis Pathologymentioning

confidence: 91%

Cellular senescence in osteoarthritis pathology

2017

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SummaryCellular senescence is a state of stable proliferation arrest of cells. 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, the persistence and accumulation of senescent cells in various tissues can also impair function and have been implicated in the pathogenesis of many age‐related diseases. Osteoarthritis (OA), a severely debilitating chronic condition characterized by progressive tissue remodeling and loss of joint function, is the most prevalent disease of the synovial joints, and increasing age is the primary OA risk factor. The profile of inflammatory and catabolic mediators present during the pathogenesis of OA is strikingly similar to the secretory profile observed in ‘classical’ senescent cells. During OA, chondrocytes (the sole cell type present within articular cartilage) exhibit increased levels of various senescence markers, such as senescence‐associated beta‐galactosidase (SAβGal) activity, telomere attrition, and accumulation of p16ink4a. This suggests the hypothesis that senescence of cells within joint tissues may play a pathological role in the causation of OA. In this review, we discuss the mechanisms by which senescent cells may predispose synovial joints to the development and/or progression of OA, as well as touching upon various epigenetic alterations associated with both OA and senescence.

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“…Our results also show that high levels of Cx43 in chondrocytes are related to an increase in senescence associated with a higher expression of p16 INK4a and high levels of p53. Recent studies highlight the importance of senescence in osteoarthritis [29][30][31][32][33] . In fact, Jeon et al published an article in Nature Medicine where they showed senescence as a new therapeutic target to treat osteoarthritis and promote the regeneration of cartilage 33,34 .…”

Section: Originalsmentioning

confidence: 99%

Regulación de la plasticidad celular y senescencia en condrocitos articulares: conexina 43 como diana terapéutica para el tratamiento de la artrosis

Varela‐Eirin

Varela-Vázquez

Blanco³

et al. 2019

Rev Osteoporos Metab Miner

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Introduction: Osteoarthritis (OA) is a degenerative musculoskeletal disease, which affects approximately the 13% of western population. Nowadays, there is no effective treatment for OA to avoid disease progression or to promote cartilage regeneration. Connexin43 (Cx43) is a transmembrane protein increased in cartilage and synovium from OA patients. Cx43 forms membrane channels that allow the exchange of molecules and ions between two adjacent cells through gap junctions (GJs), or between a cell and its environment through hemichannels. In this study we investigated the involvement of Cx43 and GJ intercellular communication in the degradation of articular cartilage in chondrocytes from patients with OA. Material and methods: Primary chondrocytes were obtained from cartilage from OA and healthy donors. Protein levels were evaluated by western-blot, immunofluorescence and flow cytometry. RNA expression was evaluated by RT-qPCR. A scrape loading/dye transfer assay was used to evaluate cell communication. Cell senescence was analysed by flow cytometry or by light microscopy using β-galactosidase assay. Results: Cx43 and GJs overactivities were correlated with the progression of OA, by promoting chronic cell dedifferentiation and senescence in vitro assays. We found that Cx43 overexpression activates factors involved in epithelial-to-mesenchymal transition, such as Twist-1. Increased levels of dedifferentiated cells, with high rates of cell proliferation, led to cell senescence via p53/p16 INK4a , activating the senescence-associated secretory phenotype (SASP) and promoting the synthesis and liberation of inflammatory factors, including the interleukin-6 (IL-6). Cx43 downregulation by using small molecules, such as oleuropein, or by genetic edition with CRISPR technology, led to the chondrocyte redifferentiation and an improved phenotype, with increased synthesis of extracellular matrix proteins such as Col2A1 and downregulating the synthesis of MMPs, inflammation and senescence. Conclusions: Downregulation of Cx43 in OA chondrocytes restores regeneration by activating chondrocyte re-differentiation and decreasing cellular senescence. These results corroborate the use of Cx43 as an effective therapeutic target in order to restore cartilage regeneration and avoid OA progression.

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Correlation between senescence‐associated beta‐galactosidase expression in articular cartilage and disease severity of patients with knee osteoarthritis

Abstract: SA-beta-Gal expression in articular cartilage is associated with progressive knee OA joint damage and is a potential indictor of disease severity.

Cited by 68 publications

References 29 publications

Senescent cells and osteoarthritis: a painful connection

Senescent cells and osteoarthritis: a painful connection

Cellular senescence in osteoarthritis pathology

Regulación de la plasticidad celular y senescencia en condrocitos articulares: conexina 43 como diana terapéutica para el tratamiento de la artrosis

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