**2. Alteration in cartilage composition in Osteoarthritis (OA)**

The chondrocyte is responsible for both the synthesis and the breakdown of the cartilaginous matrix but the mechanisms that control this balance are poorly understood [4]. The distribution of load across the joint is an important function of the articular cartilage for avoid excessive load affecting both cartilage and bone. It has been demonstrated that articular chondrocytes are able to respond to mechanical injury where biological stimuli such as cytokines and growth and differentiation factors contribute to structural changes in the surrounding cartilage matrix. It has been demonstrated that many non-mechanical and mechanical factors such as load clearly have a role in the initiation and propagation the processes of OA. The OA is the most common joint disease allowing dysfunction and pain. The OA is characterized by changes in chondrocyte metabolism that leads to elevated production of proteolytic enzymes, cartilage damage and loss of joint function. It have been described several mechanisms that can lead to OA, among of these mechanisms are mechanicals, bone changes and changes in the cartilage extracellular matrix [5, 6]

Aging, cartilage senescence and reactive oxygen species (ROS) are normal changes in the musculoskeletal system that contribute to the development of OA, but the mechanisms are poorly understood [5]. Inflammation is considered as a very early event in OA perhaps induced by joint trauma affecting chondrocytes in the cartilage and synovial cells (fibroblasts and macrophages) to produce cytokines as interleukin-1-beta (IL-1β) and tumoral necrosis factoralpha (TNF-α), and other signaling molecules as proteoglycans to switch to or increase catabolic processes [6]. Obesity has been described as a risk factor for OA by increased mechanical load factors and degenerative knee pain. The mechanisms between obesity and OA are not completly understood but, it has been found the release of fat molecules that can affect the processes in the joint, including adipokines as visfatin and leptin, perhaps affecting the inflammatory response [7, 9]. Malalignment of the knee joint plays an important role in the development of early osteoarthritis changing the center of pressure of articular cartilage and subchondral bone. Varus or valgus malalignment of the lower extremity results in an abnormal load distribution across the medial and lateral tibiofemoral compartment and being increased in patients with knee osteoarthritis and is increased in patients with overweight. However, studies examining the relationship between malalignment and early knee osteoarthritis have produced conflicting results. The association between malalignment and OA changes is based on radiographic changes mainly and different multicenter OA studies [10-12]. Meniscus is an important tissue in the system of the knee. It is function is the load transmission and absortion shock. Complete or partial loss of meniscal tissue alters the biomechanical and biological of the knee joint modifying the pattern of load distribution and the instability of the knee. Meniscal narrowing, cartilage loss and chondral lesions increase the risk of secondary OA with cartilage degeneration. This secondary OA is associated to chondral damage, ligamentous instability, and malalignment with reduction in the shock absorption capacity of the knee [13-15]. Extrussion has been associated with articular changes according to their depth into partial-thickness and full-thickens defects. Partial-thickness lesions are considered less symptomatic with little evidence of progression on osteoarthritis. Full-thickness chondral and osteochondral lesions frequently cause symptoms, and they are considered to predispose to premature osteoarthritis [16]. Osteochondritis dissecans studies have demonstrated knee joint dysfunction and high prevalence of osteoarthritic change after fragment removal and all the studies take in account the limitation of a small defect size from 1.5 to 4.0 cm2 as well the zone and the location of the defect in the cartilage [17, 18]. The anterior cruciate ligament (ACL) is the knee ligament most common disrupted. ACL lesion frequently is associated to other ligamentous structures like, menisci, the articular cartilage or subchondral plate [19, 20].
