Rheumatoid arthritis (RA) is a long-term autoimmune disorder that primarily affects joints. It typically results in warm, swollen, and painful joints. Pain and stiffness often worsen following rest. Most commonly, the wrist and hands are involved, with the same joints typically involved on both sides of the body. The disease may also affect other parts of the body, including skin, eyes, lungs, heart, nerves, and blood. This may result in a low red blood cell count, inflammation around the lungs, and inflammation around the heart. Fever and low energy may also be present. Often, symptoms come on gradually over weeks to months.
Cartilage is a resilient and smooth type of connective tissue. It is a semi-transparent and non-porous type of tissue. It is usually covered by a tough and fibrous membrane called perichondrium. In tetrapods, it covers and protects the ends of long bones at the joints as articular cartilage, and is a structural component of many body parts including the rib cage, the neck and the bronchial tubes, and the intervertebral discs. In other taxa, such as chondrichthyans, but also in cyclostomes, it may constitute a much greater proportion of the skeleton. It is not as hard and rigid as bone, but it is much stiffer and much less flexible than muscle. The matrix of cartilage is made up of glycosaminoglycans, proteoglycans, collagen fibers and, sometimes, elastin. It usually grows quicker than bone.
In biology, the extracellular matrix (ECM), also called intercellular matrix (ICM), is a network consisting of extracellular macromolecules and minerals, such as collagen, enzymes, glycoproteins and hydroxyapatite that provide structural and biochemical support to surrounding cells. Because multicellularity evolved independently in different multicellular lineages, the composition of ECM varies between multicellular structures; however, cell adhesion, cell-to-cell communication and differentiation are common functions of the ECM.
Connective tissue is one of the four primary types of animal tissue, along with epithelial tissue, muscle tissue, and nervous tissue. It develops mostly from the mesenchyme, derived from the mesoderm, the middle embryonic germ layer. Connective tissue is found in between other tissues everywhere in the body, including the nervous system. The three meninges, membranes that envelop the brain and spinal cord, are composed of connective tissue. Most types of connective tissue consists of three main components: elastic and collagen fibers, ground substance, and cells. Blood, and lymph are classed as specialized fluid connective tissues that do not contain fiber. All are immersed in the body water. The cells of connective tissue include fibroblasts, adipocytes, macrophages, mast cells and leukocytes.
A synovial joint, also known as diarthrosis, joins bones or cartilage with a fibrous joint capsule that is continuous with the periosteum of the joined bones, constitutes the outer boundary of a synovial cavity, and surrounds the bones' articulating surfaces. This joint unites long bones and permits free bone movement and greater mobility. The synovial cavity/joint is filled with synovial fluid. The joint capsule is made up of an outer layer of fibrous membrane, which keeps the bones together structurally, and an inner layer, the synovial membrane, which seals in the synovial fluid.
Synovial fluid, also called synovia,[help 1] is a viscous, non-Newtonian fluid found in the cavities of synovial joints. With its egg white–like consistency, the principal role of synovial fluid is to reduce friction between the articular cartilage of synovial joints during movement. Synovial fluid is a small component of the transcellular fluid component of extracellular fluid.
Hyaline cartilage is the glass-like (hyaline) and translucent cartilage found on many joint surfaces. It is also most commonly found in the ribs, nose, larynx, and trachea. Hyaline cartilage is pearl-gray in color, with a firm consistency and has a considerable amount of collagen. It contains no nerves or blood vessels, and its structure is relatively simple.
Hyaluronic acid, also called hyaluronan, is an anionic, nonsulfated glycosaminoglycan distributed widely throughout connective, epithelial, and neural tissues. It is unique among glycosaminoglycans as it is non-sulfated, forms in the plasma membrane instead of the Golgi apparatus, and can be very large: human synovial HA averages about 7 million Da per molecule, or about 20,000 disaccharide monomers, while other sources mention 3–4 million Da.
Crepitus is "a grating sound or sensation produced by friction between bone and cartilage or the fractured parts of a bone".
Pannus is an abnormal layer of fibrovascular tissue or granulation tissue. Common sites for pannus formation include over the cornea, over a joint surface, or on a prosthetic heart valve. Pannus may grow in a tumor-like fashion, as in joints where it may erode articular cartilage and bone.
Synovitis is the medical term for inflammation of the synovial membrane. This membrane lines joints that possess cavities, known as synovial joints. The condition is usually painful, particularly when the joint is moved. The joint usually swells due to synovial fluid collection.
Synovectomy is a procedure where the synovial tissue surrounding a joint is removed. This procedure is typically recommended to provide relief from a condition in which the synovial membrane or the joint lining becomes inflamed and irritated and is not controlled by medication alone. If arthritis is not controlled, it can lead to irreversible joint damage. The synovial membrane or "synovium" encloses each joint and also secretes a lubricating fluid that allows different joint motions such as rolling, folding and stretching. When the synovium becomes inflamed or irritated, it increases fluid production, resulting in warmth, tenderness, and swelling in and around the joint.
Aggrecan (ACAN), also known as cartilage-specific proteoglycan core protein (CSPCP) or chondroitin sulfate proteoglycan 1, is a protein that in humans is encoded by the ACAN gene. This gene is a member of the lectican (chondroitin sulfate proteoglycan) family. The encoded protein is an integral part of the extracellular matrix in cartilagenous tissue and it withstands compression in cartilage.
Osteoimmunology is a field that emerged about 40 years ago that studies the interface between the skeletal system and the immune system, comprising the "osteo-immune system". Osteoimmunology also studies the shared components and mechanisms between the two systems in vertebrates, including ligands, receptors, signaling molecules and transcription factors. Over the past decade, osteoimmunology has been investigated clinically for the treatment of bone metastases, rheumatoid arthritis (RA), osteoporosis, osteopetrosis, and periodontitis. Studies in osteoimmunology reveal relationships between molecular communication among blood cells and structural pathologies in the body.
Chitinase-3-like protein 1 (CHI3L1), also known as YKL-40, is a secreted glycoprotein that is approximately 40kDa in size that in humans is encoded by the CHI3L1 gene. The name YKL-40 is derived from the three N-terminal amino acids present on the secreted form and its molecular mass. YKL-40 is expressed and secreted by various cell-types including macrophages, chondrocytes, fibroblast-like synovial cells, vascular smooth muscle cells, and hepatic stellate cells. The biological function of YKL-40 is unclear. It is not known to have a specific receptor. Its pattern of expression is associated with pathogenic processes related to inflammation, extracellular tissue remodeling, fibrosis and solid carcinomas and asthma.
Proteoglycan 4 or lubricin is a proteoglycan that in humans is encoded by the PRG4 gene. It acts as a joint/boundary lubricant.
A rheumatoid nodule is a lump of tissue, or an area of swelling, that appears on the exterior of the skin usually around the olecranon or the interphalangeal joints, but can appear in other areas. There are four different types of rheumatoid nodules: subcutaneous rheumatoid nodules, cardiac nodules, pulmonary nodules, and central nervous systems nodules. These nodules occur almost exclusively in association with rheumatoid arthritis. Very rarely do rheumatoid nodules occur as rheumatoid nodulosis in the absence of rheumatoid arthritis. Rheumatoid nodules can also appear in areas of the body other than the skin. Less commonly they occur in the lining of the lungs or other internal organs. The occurrence of nodules in the lungs of miners exposed to silica dust was known as Caplan’s syndrome. Rarely, the nodules occur at diverse sites on body.
Fibroblast-like synoviocytes (FLS) represent a specialised cell type located inside joints in the synovium. These cells play a crucial role in the pathogenesis of chronic inflammatory diseases, such as rheumatoid arthritis.
A tissue membrane is a thin layer or sheet of cells that covers the outside of the body, the organs, internal passageways that lead to the exterior of the body, and the lining of the moveable joint cavities. There are two basic types of tissue membranes: connective tissue and epithelial membranes.
Radiosynoviorthesis (RSO) is a minimally invasive therapeutic procedure for managing joint inflammation, particularly synovitis associated with osteoarthritis. Radiosynoviorthesis involves the intra-articular injection of radioactive isotopes to specifically treat the inflamed synovial membrane. Synovitis, a hallmark of various joint disorders, including osteoarthritis, manifests as inflammation within the synovial membrane lining the joints. RSO aims to suppress overactive macrophage and synovial cells responsible for the inflammatory response, providing relief from pain and improving joint functionality.
