Epigenetic Regulation in Knee Osteoarthritis

Cai, Zhengyu; Long, Teng; Zhao, Yaochao; Lin, Ruixin; Wang, You

doi:10.3389/fgene.2022.942982

Cited by 9 publications

(9 citation statements)

References 105 publications

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“…This refreshing wave of discovery has coincided with epigenetic studies of joint tissues that have examined DNA methylation, histone modi cations, and non-coding RNAs (5,34,35). These epigenetic analyses have involved investigations of joint development, homeostasis, and disease, and have used both human samples and animal models.…”

Section: Discussionmentioning

confidence: 99%

Quantitative analysis of DNA methylation-related proteins in patients with knee osteoarthritis

Cai

Long

Wang

2023

Preprint

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Background Knee osteoarthritis is a common musculoskeletal disease characterized by degeneration of articular cartilage. Current diagnostic tools are limited to radiographs and physical examination. Methods We collected osteoarthritis cartilage tissues of five patients at different OA stage. We performed genome-wide DNA methylation sequencing and proteomic assays. For proteomic data processing, raw data from LC-MS/MS were imported into Proteome Discover 2.4 (Thermofisher) for analysis. For DNA methylation data processing, statistical differences in continuous variables between the two groups were compared by independent-samples t test. The possible causative genes were identified by cross-analysis of the two tests Results We identified 13 potential genes as osteoarthritis-related genetic signatures after analysis of the methylation and proteome. Conclusions Our study found that the process of knee osteoarthritis may be regulated by a combination of epigenetic and genetic modulation.

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Section: Discussionmentioning

confidence: 99%

Quantitative analysis of DNA methylation-related proteins in patients with knee osteoarthritis

Cai

Long

Wang

2023

Preprint

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“…CpG islands (CGIs) are regions with CpG‐rich DNA sequences, usually located within or near gene promotors (Bird, 1986 ; Bird et al., 1985 ; Saxonov et al., 2006 ), and methylation of CGIS promotors could silence gene expression (Robertson & Wolffe, 2000 ). Numerous signature genes with abnormal methylation status have been identified in OA patients (Cai et al., 2022 ). Notably, the differentiation of monocytes into osteoclasts is also influenced by both demethylation and methylation processes.…”

Section: How Do Hallmarks Of Aging Participate In the Pathogenesis Of...mentioning

confidence: 99%

Osteoclasts and osteoarthritis: Novel intervention targets and therapeutic potentials during aging

Wang,

Yuan,

Wang

et al. 2024

Aging Cell

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Osteoarthritis (OA), a chronic degenerative joint disease, is highly prevalent among the aging population, and often leads to joint pain, disability, and a diminished quality of life. Although considerable research has been conducted, the precise molecular mechanisms propelling OA pathogenesis continue to be elusive, thereby impeding the development of effective therapeutics. Notably, recent studies have revealed subchondral bone lesions precede cartilage degeneration in the early stage of OA. This development is marked by escalated osteoclast‐mediated bone resorption, subsequent imbalances in bone metabolism, accelerated bone turnover, and a decrease in bone volume, thereby contributing significantly to the pathological changes. While the role of aging hallmarks in OA has been extensively elucidated from the perspective of chondrocytes, their connection with osteoclasts is not yet fully understood. There is compelling evidence to suggest that age‐related abnormalities such as epigenetic alterations, proteostasis network disruption, cellular senescence, and mitochondrial dysfunction, can stimulate osteoclast activity. This review intends to systematically discuss how aging hallmarks contribute to OA pathogenesis, placing particular emphasis on the age‐induced shifts in osteoclast activity. It also aims to stimulate future studies probing into the pathological mechanisms and therapeutic approaches targeting osteoclasts in OA during aging.

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“…Lastly, knee OA subsets should be considered when performing genetic analyses of patients with OA. It has been challenging to identify specific genetic contributions through genome-wide scans [ 112 , 113 , 114 , 115 ], but perhaps new technologies and assessing subsets of patients (OA subtypes, sex, ethnicity) will yield more precision-based findings.…”

Section: The Way Forwardmentioning

confidence: 99%

Osteoarthritis as an Umbrella Term for Different Subsets of Humans Undergoing Joint Degeneration: The Need to Address the Differences to Develop Effective Conservative Treatments and Prevention Strategies

Hart

2022

IJMS

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Osteoarthritis (OA) of joints such as the knee and hip are very prevalent, and the number of individuals affected is expected to continue to rise. Currently, conservative treatments after OA diagnosis consist of a series of increasingly invasive interventions as the degeneration and pain increase, leading very often to joint replacement surgery. Most interventions are focused on alleviating pain, and there are no interventions currently available that stop and reverse OA-associated joint damage. For many decades OA was considered a disease of cartilage, but it is now considered a disease of the whole multi-tissue joint. As pain is the usual presenting symptom, for most patients, it is not known when the disease process was initiated and what the basis was for the initiation. The exception is post-traumatic OA which results from an overt injury to the joint that elevates the risk for OA development. This scenario leads to very long wait lists for joint replacement surgery in many jurisdictions. One aspect of why progress has been so slow in addressing the needs of patients is that OA has been used as an umbrella term that does not recognize that joint degeneration may arise from a variety of mechanistic causes that likely need separate analysis to identify interventions unique to each subtype (post-traumatic, metabolic, post-menopausal, growth and maturation associated). A second aspect of the slow pace of progress is that the bulk of research in the area is focused on post-traumatic OA (PTOA) in preclinical models that likely are not clearly relevant to human OA. That is, only ~12% of human OA is due to PTOA, but the bulk of studies investigate PTOA in rodents. Thus, much of the research community is failing the patient population affected by OA. A third aspect is that conservative treatment platforms are not specific to each OA subset, nor are they integrated into a coherent fashion for most patients. This review will discuss the literature relevant to the issues mentioned above and propose some of the directions that will be required going forward to enhance the impact of the research enterprise to affect patient outcomes.

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Epigenetic Regulation in Knee Osteoarthritis

Cited by 9 publications

References 105 publications

Quantitative analysis of DNA methylation-related proteins in patients with knee osteoarthritis

Quantitative analysis of DNA methylation-related proteins in patients with knee osteoarthritis

Osteoclasts and osteoarthritis: Novel intervention targets and therapeutic potentials during aging

Osteoarthritis as an Umbrella Term for Different Subsets of Humans Undergoing Joint Degeneration: The Need to Address the Differences to Develop Effective Conservative Treatments and Prevention Strategies

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