Risk factors and molecular entities of the etiopathogenesis of the knee osteoarthritis (literature review)

Abstract

Introduction Osteoarthritis (OA) is a heterogenic group of disorders of different etiology with similar biological, morphological and clinical manifestations and outcomes. OA is now considered a disease of the whole joint, including alterations in the articular cartilage, subchondral bone, synovial membrane, ligaments, capsule and periarticular muscles. OA of the knee as the most commonly affected joint accounts for the great medical, medical, social and economic impact. Material and methods A literature review assessing Russian and foreign studies on molecular mechanisms of etiology and pathogenesis of knee OA identified a set of factors for which there was consistent evidence for their association with onset of knee OA. A search of studies published in Russian and in English for the last ten years was conducted using bibliographic databases, including PubMed, PubMedCentral, GoogleScholar, eLIBRARY. Search terms included 'knee osteoarthritis', 'etiology', 'pathogenesis', 'risk factors'. Results Review of the literature showed that patients with knee OA are characterized by changes in cartilage, subchondral bone, synovium, suggesting common mechanisms of joint degeneration during OA development. Osteoarthritis (OA) is multifactorial in origin and closely associated with a wide spectrum of local (previous injury, muscle weakness, knee malalignment, knee surgeries, abnormal mechanical loading, excessive high impact sports, occupational physical activities) and systemic risk factors (advanced age, female sex, height, greater body mass index and obesity, hormone status, family history, mineral bone density, vitamin D deficiency, ethnicity). The prevalence of the knee OA and patterns of joint involvement vary among different racial and ethnic groups. Conclusion The literature review allowed us to identify the molecular mechanisms of etiopathogenesis of knee OA and the major risk factors for the pathology.

NFAT gene polymorphism as a risk factor of knee osteoarthrosis

“…Some data confirm a role NFAT5 gene plays in creating inborn immunity by activating gene expression in macrophages during TLR (Toll-like) receptor ligation [36,42,43]. We should note that immune disorders and inflammation of the syno-vial membranes (synovitis) are believed to contribute significantly to OA pathogenesis [2,44,45]. In future this may lead to "activation" of matrix metalloproteinases [46] that produce apparent proliferative and pro-inflammatory effects.…”

Research Progress on the Pathogenesis of Knee Osteoarthritis

“…These factors also cause and affect one another, creating a vicious cycle that results in the development of KOA. 10 Age is considered to be the most prominent risk factor for KOA development. 11 The aging of the body leads to degeneration of joint tissue, from subchondral bone dilatation, myelopathy, meniscus tear and compression, to cartilage defects, and a series of structural changes occur in the joint.…”

“…In recent years, numerous studies have demonstrated that aging, trauma, knee dislocation, obesity, increased joint weight bearing, and decreased joint stability all play a significant role in the development of KOA. These factors also cause and affect one another, creating a vicious cycle that results in the development of KOA 10 …”

“…These factors also cause and affect one another, creating a vicious cycle that results in the development of KOA. 10 …”

NFAT gene polymorphism as a risk factor of knee osteoarthrosis

“…Имеются данные, свидетельствующие о роли NFAT5 в формировании врожденного иммунитета путем активации экспрессии генов в макрофагах при лигировании TLR (Toll-like) рецептора [36,42,43]. Стоит отметить, что в патогенезе ОА коленного сустава значимая роль отводится иммунным нарушениям и воспалению синовиальной оболочки -синовиту [2,44,45], что впоследствии может приводить к «активизации» матриксных металлопротеиназ [46], обладающих выраженными пролиферативными и провоспалительными эффектами. Известно, что TLR2 и TLR4 высокоэкспрессируются в макрофагах синовиальной жидкости и отвечают за активацию макрофагов [47].…”