Cell Death and Apoptosis in Ostearthritic Cartilage

Abstract

Osteoarthritis (OA) is the most common chronic joint disease in the elderly population, causing significant pain and disability. Because the cardinal feature of OA is a progressive loss of articular cartilage, a great portion of the research endeavour into the pathogenesis of OA has been focused on the regulation of matrix synthesis and degradation. The phenotypic stability and survival of the chondrocytes are essential for the maintenance of a proper cartilage matrix. This has lead to the long-standing assumption that cell death is a central feature in OA cartilage degeneration. The important role of apoptosis in OA has been demonstrated in in vitro and in vivo models. However, it should be noted that the relative contribution of apoptotic cell death in the pathogenesis of OA is still difficult to assess because of the chronic nature of the disease process. Therefore, the apoptosis of chondrocytes seems to be a potential target for therapeutic interventions in OA. The death receptor, mitochondrial and endoplasmic reticulum pathways are the major cellular pathways of apoptosis. Of all these elements involved in the apoptosis of chondrocytes, caspase inhibition has been studied with the most detail. Other molecules with the capacity to modulate mitochondria function, phosphatase (PP-1A/B) activity and pro-apoptosis stimuli (NO, prostaglandins, cytokines, ROS) could be excellent targets to block apoptosis of chondrocytes. Finally, the regulation of the natural inhibitors of apoptosis (c-FLIP, BAR, ARC and HC-gp39) could complement the other strategies to reduce cartilage degradation.

The antioxidant resveratrol protects against chondrocyte apoptosis via effects on mitochondrial polarization and ATP production

“…Increased chondrocyte apoptosis is also considered a key pathologic feature of OA (41). Recent findings in the literature suggest that OA chondrocytes exhibit a loss of mitochondrial function, which precedes the classic signs of apoptotic cell death (2,3,42).…”

Mitochondrial DNA haplogroups: Role in the prevalence and severity of knee osteoarthritis

“…In addition, morphologic studies have described changes in mitochondria from OA chondrocytes, including nuclear and cytoplasmic changes (16), and the mitochondrial mass was shown to be increased in OA chondrocytes as compared with cells from normal cartilage (15). Furthermore, the apoptotic mitochondrial pathway has been implicated as one of the major cellular pathways of apoptosis in OA chondrocytes (17), and mitochondrial free radical production has been shown to compromise chondrocyte function (13,18). This evidence, combined with the generally recognized phenomenon of loss of function in aging mitochondria (19), leads to the conclusion that mitochondria can mediate the pathogenesis of OA.…”

Melatonina: modulador de morte celular

“…It should be noted that some proteins in the Bcl-2 family also modulate the activation of caspases, whether inhibiting the activation of these proteases, such as Bcl-2, Bcl-xl, Bcl-w, or promoting apoptosis, such as Bax, Bax, Bid, Bak and Bcl-xs 5,[24][25][26][27] .…”

“…On the other hand, this process could be inhibited by the activation of anti-apoptotic molecules (Bcl-2, FLIP) that block the appearance and evolution of these cell alterations. Thus, homeostasis (essential structural and functional balance for the survival of a cell population) depends on the balance between the activation of pro-and anti-apoptotic molecules 4,5 .…”

“…When unregulated, apoptosis could contribute to the appearance of various neoplastic, autoimmune and neurodegenerative diseases 2,5,6 .…”