Chondrocyte Apoptosis in the Pathogenesis of Osteoarthritis

Abstract

Apoptosis is a highly-regulated, active process of cell death involved in development, homeostasis and aging. Dysregulation of apoptosis leads to pathological states, such as cancer, developmental anomalies and degenerative diseases. Osteoarthritis (OA), the most common chronic joint disease in the elderly population, is characterized by progressive destruction of articular cartilage, resulting in significant disability. Because articular cartilage depends solely on its resident cells, the chondrocytes, for the maintenance of extracellular matrix, the compromising of chondrocyte function and survival would lead to the failure of the articular cartilage. The role of subchondral bone in the maintenance of proper cartilage matrix has been suggested as well, and it has been proposed that both articular cartilage and subchondral bone interact with each other in the maintenance of articular integrity and physiology. Some investigators include both articular cartilage and subchondral bone as targets for repairing joint degeneration. In late-stage OA, the cartilage becomes hypocellular, often accompanied by lacunar emptying, which has been considered as evidence that chondrocyte death is a central feature in OA progression. Apoptosis clearly occurs in osteoarthritic cartilage; however, the relative contribution of chondrocyte apoptosis in the pathogenesis of OA is difficult to evaluate, and contradictory reports exist on the rate of apoptotic chondrocytes in osteoarthritic cartilage. It is not clear whether chondrocyte apoptosis is the inducer of cartilage degeneration or a byproduct of cartilage destruction. Chondrocyte death and matrix loss may form a vicious cycle, with the progression of one aggravating the other, and the literature reveals that there is a definite correlation between the degree of cartilage damage and chondrocyte apoptosis. Because current treatments for OA act only on symptoms and do not prevent or cure OA, chondrocyte apoptosis would be a valid target to modulate cartilage degeneration.

Protective effect of controlled release of cytokine response modifier A from chitosan microspheres on rat chondrocytes from interleukin-1β induced inflammation and apoptosis

“…Apoptosis is a highly-regulated, active process of cell death that is associated with the development of human and animal OA (25). In the present study, it was revealed that CS slightly but not markedly decreased the percentage of apoptotic chondrocytes.…”

Evaluation of MiR-181a as a potential therapeutic target in osteoarthritis

“…While there are several hundred-gene targets that harbor putative miR-181a binding sites within their 3'UTR region, only few have been experimentally validated. We identified BCL2 as the target gene of interest since it is a negative regulator of apoptosis [17], a key process involved in the degeneration of cartilage during the pathogenesis of OA [19]. It was found that BCL2 expression was lower in OA cartilage as compared to normal cartilage, which is consistent with post-transcriptional suppression by miR181a.…”

Transient Receptor Potential Channel, Vanilloid 5, Induces Chondrocyte Apoptosis in a Rat Osteoarthritis Model Through the Mediation of Ca2+ Influx

“…Based on current knowledge, chondrocyte apoptosis could be the underlying factor for the initiation of OA, as well as being involved in the advanced stages of the disease [3]. Understanding the mechanism of chondrocyte apoptosis is essential for developing appropriate targeted therapies for OA treatment.…”

“…Articular cartilage depends solely on its resident cells, chondrocytes, to maintain the extracellular matrix. The cartilage is often accompanied by lacunar emptying, which is evidence that chondrocyte apoptosis is a central feature in OA progression [3]. Thus, in the progression of cartilage degeneration, finding a cause for chondrocyte apoptosis during OA may become a potential strategy against OA disease.…”