Healthy and Osteoarthritis-Affected Joints Facing the Cellular Crosstalk

Abstract

Osteoarthritis (OA) is a chronic, progressive, severely debilitating, and multifactorial joint disease that is recognized as the most common type of arthritis. During the last decade, it shows an incremental global rise in prevalence and incidence. The interaction between etiologic factors that mediate joint degradation has been explored in numerous studies. However, the underlying processes that induce OA remain obscure, largely due to the variety and complexity of these mechanisms. During synovial joint dysfunction, the osteochondral unit undergoes cellular phenotypic and functional alterations. At the cellular level, the synovial membrane is influenced by cartilage and subchondral bone cleavage fragments and extracellular matrix (ECM) degradation products from apoptotic and necrotic cells. These "foreign bodies" serve as danger-associated molecular patterns (DAMPs) that trigger innate immunity, eliciting and sustaining low-grade inflammation in the synovium. In this review, we explore the cellular and molecular communication networks established between the major joint compartments-the synovial membrane, cartilage, and subchondral bone of normal and OA-affected joints.

Keywords: articular cartilage; chondrocytes; molecular signals; osteoarthritis; osteocytes; subchondral bone; synovial membrane; synoviocytes.

Figure 1

Common sites (red circles) and risk factors for OA: age, gender, genetics, metabolic state (obesity, type 2 diabetes), joint overuse, trauma, and injury that contribute to changes in the main joint compartments, namely, the synovial membrane, cartilage, fibrocartilage of meniscus, as well as subchondral bone.

Figure 2

Schematic overview of a synovial joint structure. (A) Macroscopic view on the compartments of synovial joint. (B) The synovial membrane (upper part) in a healthy state. Composition of a healthy “osteochondral” unit (lower part), tidemark (red asterisk), and calcified cartilage (yellow asterisk).

Figure 3

Schematic overview of the OA-affected synovial joint with involvement of both “chondrosynovial” and “osteochondral units”. (A) Synovial joint depicting common changes, such as degradation of the articular cartilage, formation of subchondral bone cysts, and osteophytes (red arrows). (B) The synovial membrane (upper part) reveals hyperplasia of the lining layer, immune cell infiltration, angiogenesis, and fibrosis in the sublining layer. Alterations of the articular cartilage (lower part) include degradation of the non-calcified zone and thickening of the calcified zone (yellow asterisks), formation of free cartilage fragments, duplication of tidemark (red asterisk), alterations in the composition of cellular and extracellular matrix. Remodeling of the subchondral bone (lower part) reveals the thickening of the cortical bone plate, formation of cysts, and angiogenesis.