Chondrocytes In Vitro Systems Allowing Study of OA

Bednarczyk, Ewa

doi:10.3390/ijms231810308

Cited by 7 publications

(4 citation statements)

References 101 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…OA is an autoinflammatory disease mediated by chondrocytes involving multiple factors [ 17 ]. Chondrocytes are important factors in maintaining the homeostasis of articular cartilage [ 18 , 19 ].…”

Section: Discussionmentioning

confidence: 99%

PLXNC1 interference alleviates the inflammatory injury, apoptosis and extracellular matrix degradation of IL-1β-exposed chondrocytes via suppressing GRP78 expression

Meng,

Mao,

Jiang

et al. 2023

J Orthop Surg Res

View full text Add to dashboard Cite

Background Osteoarthritis (OA) is a frequently encountered debilitating joint disorder. Whether plexin C1 (PLXNC1) is implicated in OA is far from being investigated despite its well-documented pro-inflammatory property in human diseases. The goal of this study is to expound the specific role of PLXNC1 in OA and elaborate the probable action mechanism. Methods Firstly, PLXNC1 expression in the cartilage tissues of patients with OA was examined with GEO database. In interleukin-1beta (IL-1β)-induced OA cell model, RT-qPCR and western blotting tested the expression of PLXNC1, glucose-regulating protein 78 (GRP78) and extracellular matrix (ECM) degradation-related factors. Cell viability and inflammation were respectively judged by CCK-8 assay and RT-qPCR. TUNEL and western blotting estimated cell apoptosis. The potential binding between PLXNC1 and GRP78 was corroborated by Co-IP assay. Western blotting also tested the expression of endoplasmic reticulum stress (ERS)-associated proteins. Results As it turned out, PLXNC1 expression was elevated in the cartilage tissues of patients with OA and IL-1β-treated chondrocytes. When PLXNC1 was depleted, the viability injury, inflammation, apoptosis and ECM degradation of chondrocytes exposed to IL-1β were obstructed. Besides, GRP78 bond to PLXNC1 in IL-1β-treated chondrocytes. The ascending GRP78 expression in the chondrocytes exposed to IL-1β was depleted after PLXNC1 was silenced. Meanwhile, the impacts of PLXNC1 deficiency on the viability, inflammatory response, apoptosis, ECM degradation as well as ERS in IL-1β-exposed chondrocytes were abolished by GRP78 up-regulation. Conclusion In summary, PLXNC1 silencing might interact with and down-regulate GRP78 to mitigate the apoptosis, inflammation, and ECM degradation of IL-1β-insulted chondrocytes in OA.

show abstract

Section: Discussionmentioning

confidence: 99%

PLXNC1 interference alleviates the inflammatory injury, apoptosis and extracellular matrix degradation of IL-1β-exposed chondrocytes via suppressing GRP78 expression

Meng,

Mao,

Jiang

et al. 2023

J Orthop Surg Res

View full text Add to dashboard Cite

show abstract

“…Furthermore, the microstructure of cartilage is altered significantly, accompanied by water loss and degeneration of collagen fibers [29]. With increased OA severity, the synthesis and catabolism of cartilage are seriously unbalanced, coupled with the further increase and accumulation of MMPs, which aggravates the degradation of ECM [30]. Herein, similar to data presented by Xu [31], enhanced OS and inflammation were observed in AGEs-stimulated chondrocytes, which were markedly alleviated by Cabozantinib, implying that damage to chondrocytes by AGEs was signally relieved by Cabozantinib.…”

Section: Discussionmentioning

confidence: 99%

Cabozantinib prevents AGEs-induced degradation of type 2 collagen and aggrecan in human chondrocytes

Dong,

Lin,

et al. 2023

Aging

View full text Add to dashboard Cite

Osteoarthritis (OA) is a joint degenerative disease commonly observed in the old population, lacks effective therapeutic methods, and markedly impacts the normal lives of patients. Degradation of extracellular matrix (ECM) is reported to participate in OA development, which is a potential target for treating OA. Cabozantinib is an inhibitor of tyrosine kinases and is recently claimed with suppressive properties against inflammation. Herein, the protective function of Cabozantinib on advanced glycation end products (AGEs)-induced damages to chondrocytes was tested. SW1353 chondrocytes were stimulated with 100 μg/ml AGEs with or without 10 and 20 μM Cabozantinib for 24 h. Signally increased reactive oxygen species (ROS) levels, declined reduced glutathione (GSH) levels, and elevated release of inflammatory cytokines were observed in AGEs-stimulated SW1353 chondrocytes, which were markedly reversed by Cabozantinib. Moreover, the notably reduced type II collagen and aggrecan levels, and increased matrix metalloproteinase-13 (MMP-13) and A Disintegrin and Metalloproteinase with Thrombospondin Motifs-5 (ADAMTS-5) levels in AGEs-stimulated SW1353 chondrocytes were largely rescued by Cabozantinib. The downregulated Sry-type high-mobility-group box 9 (SOX-9) observed in AGEs-stimulated SW1353 chondrocytes was abolished by Cabozantinib. Furthermore, the impact of Cabozantinib on type II collagen and aggrecan levels in AGEs-treated SW1353 chondrocytes was abrogated by silencing SOX-9. Collectively, Cabozantinib prevented AGEs-induced degradation of type 2 collagen and aggrecan in human chondrocytes by mediating SOX-9.

show abstract

“…These models recapitulate several alterations in OA, including (i) increased inflammatory mediators (IL-1 β, TNF-α, COX-2, etc. ); (ii) the low synthesis of typical ECM molecules (Coll II, proteoglycans, sulphated GAG, HA and aggrecan) and inhibitors of matrix degradative enzymes such as tissue inhibitors of metalloproteinases (TIMPs); and (iii) an increased presence of catabolic mediators (collagen I and X and proteases such as MMPs and ADAMTSs) [109,110]. Notably, studies on articular chondrocytes of both human and animal species have shown the effect of n-3 PUFAs (DHA, EPA, ALA, RvD1 and PDX) in reversing the inflammation-induced up-regulation of catabolic mediators [65,[111][112][113][114][115][116] and in fostering the synthesis of anabolic markers [60,111].…”

Section: Effect Of N-3 Pufas In Oboa: Focus On Anti-inflammatory and ...mentioning

confidence: 99%

Targeting the Inflammatory Hallmarks of Obesity-Associated Osteoarthritis: Towards Nutraceutical-Oriented Preventive and Complementary Therapeutic Strategies Based on n-3 Polyunsaturated Fatty Acids

Gambari

Cellamare

Grassi

et al. 2023

IJMS

View full text Add to dashboard Cite

Obesity (Ob), which has dramatically increased in the last decade, is one of the main risk factors that contribute to the incidence and progression of osteoarthritis (OA). Targeting the characteristics of obesity-associated osteoarthritis (ObOA) may offer new chances for precision medicine strategies in this patient cohort. First, this review outlines how the medical perspective of ObOA has shifted from a focus on biomechanics to the significant contribution of inflammation, mainly mediated by changes in the adipose tissue metabolism through the release of adipokines and the modification of fatty acid (FA) compositions in joint tissues. Preclinical and clinical studies on n-3 polyunsaturated FAs (PUFAs) are critically reviewed to outline the strengths and weaknesses of n-3 PUFAs’ role in alleviating inflammatory, catabolic and painful processes. Emphasis is placed on potential preventive and therapeutic nutritional strategies based on n-3 PUFAs, with a focus on ObOA patients who could specifically benefit from reformulating the dietary composition of FAs towards a protective phenotype. Finally, tissue engineering approaches that involve the delivery of n-3 PUFAs directly into the joint are explored to address the perspectives and current limitations, such as safety and stability issues, for implementing preventive and therapeutic strategies based on dietary compounds in ObOA patients.

show abstract

Chondrocytes In Vitro Systems Allowing Study of OA

Cited by 7 publications

References 101 publications

PLXNC1 interference alleviates the inflammatory injury, apoptosis and extracellular matrix degradation of IL-1β-exposed chondrocytes via suppressing GRP78 expression

PLXNC1 interference alleviates the inflammatory injury, apoptosis and extracellular matrix degradation of IL-1β-exposed chondrocytes via suppressing GRP78 expression

Cabozantinib prevents AGEs-induced degradation of type 2 collagen and aggrecan in human chondrocytes

Targeting the Inflammatory Hallmarks of Obesity-Associated Osteoarthritis: Towards Nutraceutical-Oriented Preventive and Complementary Therapeutic Strategies Based on n-3 Polyunsaturated Fatty Acids

Contact Info

Product

Resources

About