The Role of Fibrosis in Osteoarthritis Progression

Abstract

Osteoarthritis (OA) is a chronic degenerative joint disease where the main characteristics include cartilage degeneration and synovial membrane inflammation. These changes in the knee joint eventually dampen the function of the joint and restrict joint movement, which eventually leads to a stage where total joint replacement is the only treatment option. While much is still unknown about the pathogenesis and progression mechanism of OA, joint fibrosis can be a critical issue for better understanding this disease. Synovial fibrosis and the generation of fibrocartilage are the two main fibrosis-related characteristics that can be found in OA. However, these two processes remain mostly misunderstood. In this review, we focus on the fibrosis process in OA, especially in the cartilage and the synovium tissue, which are the main tissues involved in OA.

Keywords: articular cartilage; chondrocyte; fibrosis; osteoarthritis; synoviocyte; synovium.

Figure 1

Fibrosis in synovial and cartilage tissue. (A) The normal joint consists of a smooth layer of articular cartilage and a smooth layer of synovial membrane on the side that maintains the synovial fluid in the synovial cavity. In the joint of a patient with osteoarthritis (OA), the increased proliferation of synovial cells induces synovial fibrosis that results in joint swelling, stiffness, and pain. The increasing levels of synovium eventually affect the cartilage and bone tissue, inducing further degradation of the cartilage tissue and bone erosion. (B) The normal articular cartilage has a smooth extracellular matrix (ECM) that is mostly composed of aggrecan and collagen type II. Normally, chondrocytes remain in small spaces called lacunae. However, chondrocytes in a defected cartilage lesion undergo abnormal proliferation that leads to their de-differentiation into fibroblast-like fibrotic chondrocytes. Then, these chondrocytes secrete ECM proteins such as collagen type I instead of aggrecan or collagen type II. These changes lead to a stiffer type of cartilage and eventually completely change the characteristics of the articular cartilage.

Figure 2

Chondrocyte de-differentiation process in cartilage lesion. (A) When cartilage damage occurs, (B) chondrocytes that are embedded near the lesion become actively proliferative and start to change the surrounding environment by synthesizing collagen type I. (C) The proliferative chondrocytes eventually alter into a fibroblast-like characteristics and form a thick layer of fibrocartilage-like tissue and induce degradation and dedifferentiation in the nearby hyaline cartilage tissue.

Figure 3

The process of synovial fibrosis. (A) After cartilage damage occurs, (B) the abnormally proliferative chondrocytes near the lesion secrete pro-inflammatory factors that inflames the synovial membrane. (C) The pro-inflammatory factors eventually lead to hyperplasia of the synoviocytes and thicken the lining of the synovial membrane.