# Osteoarthritis--The Role of Mesenchymal Stem Cells in Cartilage Regeneration
## 2 Etiopathogenesis  
OA is distinguished by the degradation of cartilage in the joints and the thickening of subchondral bone, accompanied by the formation of osteophytes, inflammation of the synovial membrane, degeneration of ligaments, and enlargement of the joint capsule [7]. OA is not a dormant degenerative disease but rather a dynamic disease resulting from an imbalance between joint healing and destruction [18]. The most prevalent type of joint afflicted by OA [19] is the synovial joint (diarthrosis), often known as \"freely moveable joints\". As a non-neuronal, non-lymphatic, and non-vascular connective tissue, joint cartilage is incapable of self-healing. The primary function of shock absorption is to mitigate the impact of bone collisions by distributing stress uniformly throughout the joints during weight-bearing activities, including walking, weightlifting, and high-intensity workouts such as sprinting and leaping. Two to four millimeters of hyaline cartilage on healthy human joint surfaces are present. A microgram of wet cartilage typically consists of around 65-85% water, 12-24% collagen, 3-6% glycosaminoglycans (GAG), and a population of 16,000-90,000 chondrocytes. The regulation of the biomechanical characteristics of joint cartilage is influenced by the content and integrity of the extracellular fluid (ECF) [20]. Deterioration of the articular cartilage and the bones that support it is what leads to the onset of OA. Cartilage is an important structural element found throughout the human body. It is made up of cells that are referred to as chondrocytes, cells that regulate, produce, and repair articular cartilage [8; 19; 21]. ECM is composed of collagen, elastin, and proteoglyph fibers. These chondrocytes produce a great deal of ECM. Under typical situations, this matrix is constantly evolving. This process is governed by matrix metalloproteinases (MMPs), which activate latent enzymes. These MMPs are released as inactive proenzymes, which another enzyme must cleave in order to become active. Alpha-2-macroglobulin, derived from blood, and MMPs tissue inhibitors (TIMPs), which are obtained from synovial and chondrocyte cells, can block active MMPs [22; 23]. OA is caused by overproducing the MMPs that break down collagen and gelatin. Because of this, the equilibrium is tipped in favor of the matrix being broken down, which ultimately leads to the loss of collagen and proteoglycan. In response, chondrocytes increase their production of proteoglycan and collagen when they detect a deficiency. Irritants, such as interleukin-1 beta (IL-18) and tumor necrosis factor-alpha (TNF-\(\alpha\)), are found in the body. They stimulate catabolic pathways and keep OA from getting better. However, as the disease progresses, remedial measures are overtaken by the gradual deterioration of cartilage. This leads to the progression of the disease, which makes the cartilage on the ends of the bones soft, prickly, and rough, and it breaks down over time. Joint linings may develop inflammation and thickening. Because the muscles around the joint become weak, the nerves become more sensitive. Such changes can make it hard to move and cause pain [23; 24]. S synovial fluid and subchondral bone nourish the joint via diffusion during normal articular mobility. As a result of joint movement, synovial fluid enters and exits the synovial joint cartilage, delivering nutrients and eliminating waste [25]. The proximal subchondral bone provides the cartilage with glucose, oxygen, and water via thick capillaries in the region [26]. Hence, the interaction and involvement of cartilage, subchondral bone, and synovium are of utmost importance in developing osteoarthritis, particularly in aberrant joint mechanics [19]. Although the etiology is not entirely understood, genetic, constitutional, and environmental factors are considered [27]. Age, gender, a previous joint injury, overweight, genetic weakness, and mechanical factors are the most common risk factors [9].