Interplay between cartilage and subchondral bone contributing to pathogenesis of osteoarthritis

Abstract

Osteoarthritis (OA) is a common debilitating joint disorder, affecting large sections of the population with significant disability and impaired quality of life. During OA, functional units of joints comprising cartilage and subchondral bone undergo uncontrolled catabolic and anabolic remodeling processes to adapt to local biochemical and biological signals. Changes in cartilage and subchondral bone are not merely secondary manifestations of OA but are active components of the disease, contributing to its severity. Increased vascularization and formation of microcracks in joints during OA have suggested the facilitation of molecules from cartilage to bone and vice versa. Observations from recent studies support the view that both cartilage and subchondral bone can communicate with each other through regulation of signaling pathways for joint homeostasis under pathological conditions. In this review we have tried to summarize the current knowledge on the major signaling pathways that could control the cartilage-bone biochemical unit in joints and participate in intercellular communication between cartilage and subchondral bone during the process of OA. An understanding of molecular communication that regulates the functional behavior of chondrocytes and osteoblasts in both physiological and pathological conditions may lead to development of more effective strategies for treating OA patients.

Figure 1

A schematic diagram demonstrating the anatomy of articular cartilage and subchondral bone in normal and osteoarthritis (OA) joints. Normal articular cartilage is divided into superficial tangential zone, middle zone, deep zone, and calcified cartilage zone. These zones consist of a small number of chondrocytes trapped in collagen matrix. Calcified cartilage is separated by a tidemark from the deep zone, and rests directly on subchondral bone. Subchondral bone beneath the articular cartilage is organized into two layers: cortical plate and cancellous bone. Subchondral bone helps to maintain the integrity of the overlying articular cartilage. Alteration in OA joint is represented by collagen matrix disruption in articular cartilage and thickening of subchondral bone. Fissuring and flanking in articular cartilage induces vascularization of cartilage, leading to exposure of subchondral bone to external surface. Microcracks in the subchondral bone contribute to reactivation and upward shifting of the tidemark (demarcation line), representing thin articular cartilage with thick subchondral cortical plate. Subchondral sclerosis is a hall mark of progressive OA. (Figure produced using Servier Medical Art [17]).

Figure 2

Schematic diagram representing possible interaction of antagonists of WNT and BMP signaling pathways during progression of OA.