Osteoarthritis year in review: genetics, genomics, epigenetics

Ratneswaran, A.; Kapoor, Mohit

doi:10.1016/j.joca.2020.11.003

Cited by 54 publications

(45 citation statements)

References 94 publications

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“…Osteoarthritis (OA) is the most common degenerative musculoskeletal disorder that affects the entire joint. Its main symptoms are chronic pain, functional limitation, instability, and deformity, with a considerable reduction in quality of life; therefore, OA is considered the leading cause of disability and impairment in middle-aged and older people worldwide and represents a real burden to health care systems [1,2]. The pathogenesis of OA is complex and remains largely unknown; however, it is assumed that multiple factors including aging, gender, joint injury, obesity, and metabolic factors contribute to the onset and the progression of the disease [1].…”

Section: Introductionmentioning

confidence: 99%

A Combination of Celecoxib and Glucosamine Sulfate Has Anti-Inflammatory and Chondroprotective Effects: Results from an In Vitro Study on Human Osteoarthritic Chondrocytes

Cheleschi

Tenti

Giannotti

et al. 2021

IJMS

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This study investigated the possible anti-inflammatory and chondroprotective effects of a combination of celecoxib and prescription-grade glucosamine sulfate (GS) in human osteoarthritic (OA) chondrocytes and their possible mechanism of action. Chondrocytes were treated with celecoxib (1.85 µM) and GS (9 µM), alone or in combination with IL-1β (10 ng/mL) and a specific nuclear factor (NF)-κB inhibitor (BAY-11-7082, 1 µM). Gene expression and release of some pro-inflammatory mediators, metalloproteinases (MMPs), and type II collagen (Col2a1) were evaluated by qRT-PCR and ELISA; apoptosis and mitochondrial superoxide anion production were assessed by cytometry; B-cell lymphoma (BCL)2, antioxidant enzymes, and p50 and p65 NF-κB subunits were analyzed by qRT-PCR. Celecoxib and GS alone or co-incubated with IL-1β significantly reduced expression and release of cyclooxygenase (COX)-2, prostaglandin (PG)E2, IL-1β, IL-6, tumor necrosis factor (TNF)-α, and MMPs, while it increased Col2a1, compared to baseline or IL-1β. Both drugs reduced apoptosis and superoxide production; reduced the expression of superoxide dismutase, catalase, and nuclear factor erythroid; increased BCL2; and limited p50 and p65. Celecoxib and GS combination demonstrated an increased inhibitory effect on IL-1β than that observed by each single treatment. Drugs effects were potentiated by pre-incubation with BAY-11-7082. Our results demonstrated the synergistic effect of celecoxib and GS on OA chondrocyte metabolism, apoptosis, and oxidative stress through the modulation of the NF-κB pathway, supporting their combined use for the treatment of OA.

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Section: Introductionmentioning

confidence: 99%

A Combination of Celecoxib and Glucosamine Sulfate Has Anti-Inflammatory and Chondroprotective Effects: Results from an In Vitro Study on Human Osteoarthritic Chondrocytes

Cheleschi

Tenti

Giannotti

et al. 2021

IJMS

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“…Concerning the large body of available literature and comprehensive reviews on the RNA-RNA interactions of lncRNAs ( i.e. , ceRNA mechanisms)[ 88 , 89 ], this topic of epigenetics is not discussed in this review, but it is worth mentioning that in some cases, ceRNA mechanisms act as mediators between lncRNAs and epigenetic modifiers. Another potential involvement of lncRNAs in epigenetics is the interaction with the key enzyme of methyl metabolism.…”

Section: Discussionmentioning

confidence: 99%

Epigenetic regulation by long noncoding RNAs in osteo-/adipogenic differentiation of mesenchymal stromal cells and degenerative bone diseases

Xia¹,

Yu²,

Huang³

et al. 2022

WJSC

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Bone is a complex tissue that undergoes constant remodeling to maintain homeostasis, which requires coordinated multilineage differentiation and proper proliferation of mesenchymal stromal cells (MSCs). Mounting evidence indicates that a disturbance of bone homeostasis can trigger degenerative bone diseases, including osteoporosis and osteoarthritis. In addition to conventional genetic modifications, epigenetic modifications ( i.e. , DNA methylation, histone modifications, and the expression of noncoding RNAs) are considered to be contributing factors that affect bone homeostasis. Long noncoding RNAs (lncRNAs) were previously regarded as ‘transcriptional noise’ with no biological functions. However, substantial evidence suggests that lncRNAs have roles in the epigenetic regulation of biological processes in MSCs and related diseases. In this review, we summarized the interactions between lncRNAs and epigenetic modifiers associated with osteo-/adipogenic differentiation of MSCs and the pathogenesis of degenerative bone diseases and highlighted promising lncRNA-based diagnostic and therapeutic targets for bone diseases.

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“…OA emanates from the dysfunction of the whole joint, especially affecting the articular cartilage, synovium and subchondral bone, and tissues with close mechanical and molecular biological interactions [ 2 , 3 , 4 ]. In addition, OA is characterized by a strong hereditary background [ 5 ]. Variant alleles of several genes, often strongly expressed in cartilage, mostly lead to increased risk of developing hip or knee OA.…”

Section: Introductionmentioning

confidence: 99%

Osteoarthritis: Novel Molecular Mechanisms Increase Our Understanding of the Disease Pathology

Grässel

Zaucke

Madry

2021

JCM

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Although osteoarthritis (OA) is the most common musculoskeletal condition that causes significant health and social problems worldwide, its exact etiology is still unclear. With an aging and increasingly obese population, OA is becoming even more prevalent than in previous decades. Up to 35% of the world’s population over 60 years of age suffers from symptomatic (painful, disabling) OA. The disease poses a tremendous economic burden on the health-care system and society for diagnosis, treatment, sick leave, rehabilitation, and early retirement. Most patients also experience sleep disturbances, reduced capability for exercising, lifting, and walking and are less capable of working, and maintaining an independent lifestyle. For patients, the major problem is disability, resulting from joint tissue destruction and pain. So far, there is no therapy available that effectively arrests structural deterioration of cartilage and bone or is able to successfully reverse any of the existing structural defects. Here, we elucidate novel concepts and hypotheses regarding disease progression and pathology, which are relevant for understanding underlying the molecular mechanisms as a prerequisite for future therapeutic approaches. Emphasis is placed on topographical modeling of the disease, the role of proteases and cytokines in OA, and the impact of the peripheral nervous system and its neuropeptides.

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Osteoarthritis year in review: genetics, genomics, epigenetics

Cited by 54 publications

References 94 publications

A Combination of Celecoxib and Glucosamine Sulfate Has Anti-Inflammatory and Chondroprotective Effects: Results from an In Vitro Study on Human Osteoarthritic Chondrocytes

A Combination of Celecoxib and Glucosamine Sulfate Has Anti-Inflammatory and Chondroprotective Effects: Results from an In Vitro Study on Human Osteoarthritic Chondrocytes

Epigenetic regulation by long noncoding RNAs in osteo-/adipogenic differentiation of mesenchymal stromal cells and degenerative bone diseases

Osteoarthritis: Novel Molecular Mechanisms Increase Our Understanding of the Disease Pathology

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