Low-grade inflammation as a key mediator of the pathogenesis of osteoarthritis

Abstract

Osteoarthritis (OA) has long been viewed as a degenerative disease of cartilage, but accumulating evidence indicates that inflammation has a critical role in its pathogenesis. Furthermore, we now appreciate that OA pathogenesis involves not only breakdown of cartilage, but also remodelling of the underlying bone, formation of ectopic bone, hypertrophy of the joint capsule, and inflammation of the synovial lining. That is, OA is a disorder of the joint as a whole, with inflammation driving many pathologic changes. The inflammation in OA is distinct from that in rheumatoid arthritis and other autoimmune diseases: it is chronic, comparatively low-grade, and mediated primarily by the innate immune system. Current treatments for OA only control the symptoms, and none has been FDA-approved for the prevention or slowing of disease progression. However, increasing insight into the inflammatory underpinnings of OA holds promise for the development of new, disease-modifying therapies. Indeed, several anti-inflammatory therapies have shown promise in animal models of OA. Further work is needed to identify effective inhibitors of the low-grade inflammation in OA, and to determine whether therapies that target this inflammation can prevent or slow the development and progression of the disease.

Knee osteoarthritis has doubled in prevalence since the mid-20th century

“…Less physically active individuals who load their joints less develop thinner cartilage with lower proteoglycan content (34,35) as well as weaker muscles responsible for protecting joints by stabilizing them and limiting joint reaction forces (36). Chronic low-grade inflammation, which is exacerbated by physical inactivity (37), modern diets rich in highly refined carbohydrates (38), and excessive adiposity (10), can further magnify and accelerate loading-induced damage to joint tissues and may also directly affect knee OA pathogenesis (5). Evaluating which of these or additional features of modern environments are responsible for today's high knee OA levels is necessary.…”

“…Knee OA accounts for more than 80% of the disease's total burden (2) and affects at least 19% of American adults aged 45 y and older (3). Substantial evidence indicates that knee OA is proximately caused by the breakdown of joint tissues from mechanical loading (4) and inflammation (5), but the deeper underlying causes of knee OA's high prevalence remain unclear and poorly tested, hindering efforts to prevent and treat the disease. Two recent public health trends, however, are commonly assumed to be dominant factors (6,7).…”

Osteoarthritis: Current Clinical Concept and Some Promising Therapeutic Approaches

“…Учитывая важную роль воспаления в патогенезе ОА, одним из центральных элементов лечения этого заболева-ния, особенно на ранних стадиях его развития, следует считать противовоспалительную терапию [13][14][15]. Вероят-но, во многих случаях с этой целью могут использоваться нестероидные противовоспалительные препараты (НПВП) [47].…”

“…1). В настоящее время уже не вызывает сомне-ний, что именно хроническое низкоинтенсивное («low-grade») воспаление выступает в роли важнейшего фактора развития и прогрессирования ОА [13][14][15].…”

“…Это может быть генетически де-терминированное или приобретенное нарушение регуля-ции воспаления, при котором «провоспалительные» кле-точные и гуморальные стимулы отчетливо преобладают над «противовоспалительными» [13,14,23]. Причинами хронизации воспаления также становятся стойкие струк-турные и биомеханические нарушения, способствующие развитию механического клеточного стресса в структурах сустава даже при физиологической нагрузке.…”