Fibroblast-like synoviocyte

Fibroblast-like synoviocytes (FLS) are specialized cells found in the synovium, the inner lining of joints, and play a pivotal role in the pathogenesis of chronic inflammatory diseases, such as rheumatoid arthritis (RA). These cells are important for maintaining the homeostasis of the joint, but their dysregulation can contribute to joint damage and disease progression.

Fibroblast-like synoviocytes in Normal Tissues

The synovium, also referred to as the synovial membrane, is a thin layer of tissue that lines the joint cavity. It is situated between the joint capsule and the joint cavity, and its primary function is to produce synovial fluid. Synovial fluid, a clear, viscous liquid, lubricates the joints and reduces friction between the cartilages during movement. In addition to lubrication, the synovium provides structural support to the joint and delivers necessary nutrients to the surrounding cartilage.

The synovial membrane is organized into two layers:

• Subintima – The outer layer.
• Intima – The inner layer, which contains specialized cells that maintain joint function.

The inner layer of the synovium consists of two primary cell types: macrophage-like synovial cells and fibroblast-like synoviocytes. These cells are crucial for maintaining the internal environment of the joint. Fibroblast-like synoviocytes are responsible for the production of key components of the synovial fluid, such as hyaluronic acid and other glycoproteins.

Fibroblast-like synoviocytes are mesenchymal cells that share many characteristics with fibroblasts, such as the expression of various collagen types and vimentin, a protein that is part of the cytoskeleton. However, these cells also produce unique proteins, such as lubricin, which plays an essential role in joint lubrication. In addition, they express several molecules critical for cell adhesion, including cadherin-11, VCAM-1, and various integrins and their receptors. One distinctive feature of fibroblast-like synoviocytes is the expression of CD55, a protein commonly used in immunohistochemistry to identify these cells in the synovium.

Role of Fibroblast-like Synoviocytes in Rheumatoid Arthritis

Rheumatoid arthritis (RA) is an autoimmune disease characterized by chronic inflammation and synovial hyperplasia, where the number of synovial cells increases significantly. In RA, the synovium becomes the site of persistent inflammatory activity, leading to cartilage destruction and joint deformation. During disease progression, the number of fibroblast-like synoviocytes in the synovium increases, contributing to the inflammatory environment and subsequent joint damage.

Fibroblast-like synoviocytes in RA display a distinct phenotype compared to those in normal tissues. In RA, these cells lose the phenomenon of contact inhibition, a process in which cell growth is halted when cells come into contact with one another. Additionally, fibroblast-like synoviocytes in RA no longer depend on adhesive surfaces for growth, a characteristic that is also seen in cancer cells. These changes promote the unchecked proliferation of fibroblast-like synoviocytes in the inflamed synovium.

Furthermore, these cells produce a variety of pro-inflammatory signaling molecules that exacerbate the inflammatory response. Key molecules include:

• Interleukin 6 (IL-6)
• Interleukin 8 (IL-8)
• Prostanoids
• Matrix metalloproteinases (MMPs)

These molecules can act on other cell types in the synovium and contribute to the amplification of the inflammatory cascade, ultimately leading to the destruction of cartilage and bone.

In addition to these factors, microvesicles derived from platelets can further activate fibroblast-like synoviocytes by releasing IL-1. This process underscores the complex interplay between various immune cells and fibroblast-like synoviocytes in the progression of RA.

See Also

• Rheumatoid arthritis
• Synovium
• Fibroblasts
• Cartilage destruction
• Interleukins
• Matrix metalloproteinases

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