Osteoarthritis of the Knee

Sharma, Leena

doi:10.1056/nejmcp1903768

Cited by 608 publications

(472 citation statements)

References 53 publications

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“…Osteoarthritis (OA) is a disease of the entire joint including structural changes in articular cartilage, subchondral bone, ligaments, joint capsule, synovium, and muscles around the joint [ 1 , 2 ]. OA affects 7% of the global population and more than 500 million people.…”

Section: Introductionmentioning

confidence: 99%

The Role of Extracellular Vesicles in the Pathogenesis, Diagnosis, and Treatment of Osteoarthritis

2021

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Osteoarthritis (OA) is a degenerative joint disease that affects the entire joint and has been a tremendous burden on the health care system worldwide. Although cell therapy has made significant progress in the treatment of OA and cartilage regeneration, there are still a series of problems. Recently, more and more evidence shows that extracellular vesicles (EVs) play an important role in the progression and treatment of OA. Here, we discuss that EVs from different cell sources not only participate in OA progression, but can also be used as effective tools for the diagnosis and treatment of OA. In addition, cell pretreatment strategies and EV tissue engineering play an increasingly prominent role in the field of OA treatment. This article will systematically review the latest developments in these areas. As stated above, it may provide new insights for improving OA and cartilage regeneration.

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Section: Introductionmentioning

confidence: 99%

The Role of Extracellular Vesicles in the Pathogenesis, Diagnosis, and Treatment of Osteoarthritis

2021

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“…OA is the most common chronic joint disease in orthopedics, characterized by joint degeneration and synovial and cartilage hyperplasia, which is related to many factors such as age ( Liu et al, 2019a ; Wang et al, 2019b ). It often manifests as articular cartilage degeneration and secondary bone hyperplasia ( Sharma, 2021 ). The traditional concept believes that the biomechanical changes and biochemical factors in the joint cause the destruction of articular cartilage, resulting in OA ( Zheng et al, 2021 ).…”

Section: Discussionmentioning

confidence: 99%

HTR2B and SLC5A3 Are Specific Markers in Age-Related Osteoarthritis and Involved in Apoptosis and Inflammation of Osteoarthritis Synovial Cells

Fan

et al. 2021

Front. Mol. Biosci.

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Objective: Osteoarthritis (OA) is a heterogeneous age-related disease, which is badly difficult to cure due to its complex regulatory networks of pathogenesis. This study explored OA-specific genes in synovial tissues and validated their roles on apoptosis and inflammation of OA synovial cells.Methods: Weighted correlation network analysis (WGCNA) was employed to explore OA-related co-expression modules in the GSE55235 and GSE55457 datasets. Then, this study screened OA-specific genes. After validation of these genes in the GSE12021 and GSE32317 datasets, HTR2B and SLC5A3 were obtained. Their expression was detected in human OA and healthy synovial tissues by RT-qPCR and western blot. OA rat models were constructed by anterior cruciate ligament transection (ACLT) operation. In OA synovial cells, HTR2B and SLC5A3 proteins were examined via western blot. After transfection with sh-HTR2B or sh-SLC5A3, apoptosis and inflammation of OA synovial cells were investigated by flow cytometry and western blot.Results: A total of 17 OA-specific DEGs were identified, which were significantly enriched in inflammation pathways. Among them, HTR2B and SLC5A3 were highly expressed in end-than early-stage OA. Their up-regulation was validated in human OA synovial tissues and ACLT-induced OA synovial cells. Knockdown of HTR2B and SLC5A3 restrained apoptosis and increased TGF-β and IL-4 expression as well as reduced TNF-α and IL-1β expression in OA synovial cells.Conclusion: Collectively, this study identified two OA-specific markers HTR2B and SLC5A3 and their knockdown ameliorated apoptosis and inflammation of OA synovial cells.

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“…Osteoarthritis (OA) is a joint degenerative disease that has a strong impact on the quality of life in elderly individuals, leading to reduced mobility, pain, and even disability. This disease also adds a heavy burden to health care systems (Hunter et al, 2014;Sharma, 2021). OA is characterized by the destruction of cartilage, including aberrant chondrocyte metabolism, and degradation of the extracellular matrix (Evans, 2018).…”

Section: Introductionmentioning

confidence: 99%

IRE1-mTOR-PERK Axis Coordinates Autophagy and ER Stress-Apoptosis Induced by P2X7-Mediated Ca2+ Influx in Osteoarthritis

Huang

Zhang

et al. 2021

Front. Cell Dev. Biol.

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Moderate-intensity exercise can help delay the development of osteoarthritis (OA). Previous studies have shown that the purinergic receptor P2X ligand gated ion channel 7 (P2X7) is involved in OA development and progression. To investigate the effect of exercise on P2X7 activation and downstream signaling in OA, we used the anterior cruciate ligament transection (ACLT)-induced OA rat model and primary chondrocyte culture system. Our in vivo experiments confirmed that treadmill exercise increased P2X7 expression and that this effect was more pronounced at the later time points. Furthermore, P2X7 activation induced endoplasmic reticulum (ER) stress and increased the expression levels of ER stress markers, such as 78 kDa glucose-regulated protein (GRP78), protein kinase R-like endoplasmic reticulum kinase (PERK), inositol-requiring enzyme-1 (IRE1), and activating transcription factor 6 (ATF6). At the early time points, IRE1 and PERK were activated, and mTOR was inhibited. At the later time points, mTOR was activated, mediating PERK to promote ER stress-apoptosis, whereas IRE1 and autophagy were inhibited. To confirm our observations in vitro, we treated primary chondrocytes with the P2X7 agonist benzoylbenzoyl-ATP (Bz-ATP). Our results confirmed that P2X7-mediated Ca2+ influx activated IRE1-mediated autophagic flux and induced PERK-mediated ER stress-apoptosis. To further investigate the role of P2X7 in OA, we injected mTOR antagonist rapamycin or P2X7 antagonist A740003 into the knee joints of ACLT rats. Our results demonstrated that mTOR inhibition induced autophagy, decreased apoptosis, and reduced cartilage loss. However, injection of mTOR agonist MHY1485 or Bz-ATP had the opposite effect. In summary, our results indicated that during the early stages of moderate-intensity exercise, P2X7 was activated and autophagic flux was increased, delaying OA development. At the later stages, P2X7 became over-activated, and the number of apoptotic cells increased, promoting OA development. We propose that the IRE1-mTOR-PERK signaling axis was involved in the regulation of autophagy inhibition and the induction of apoptosis. Our findings provide novel insights into the positive and preventative effects of exercise on OA, suggesting that the intensity and duration of exercise play a critical role. We also demonstrated that on a molecular level, P2X7 and its downstream pathways could be potential therapeutic targets for OA.

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Osteoarthritis of the Knee

Cited by 608 publications

References 53 publications

The Role of Extracellular Vesicles in the Pathogenesis, Diagnosis, and Treatment of Osteoarthritis

The Role of Extracellular Vesicles in the Pathogenesis, Diagnosis, and Treatment of Osteoarthritis

HTR2B and SLC5A3 Are Specific Markers in Age-Related Osteoarthritis and Involved in Apoptosis and Inflammation of Osteoarthritis Synovial Cells

IRE1-mTOR-PERK Axis Coordinates Autophagy and ER Stress-Apoptosis Induced by P2X7-Mediated Ca2+ Influx in Osteoarthritis

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