Cell death of chondrocytes is a combination between apoptosis and autophagy during the pathogenesis of Osteoarthritis within an experimental model

Abstract

The death of chondrocytes and the loss of extracellular matrix are the central features in cartilage degeneration during Osteoarthritis (OA) pathogenesis. The mechanism by which chondrocytes are removed in OA cartilage are still not totally defined, although previous reports support the presence of apoptotic as well as non apoptotic signals. In addition, in 2004 Roach and co-workers suggested the term "Chondroptosis" to design the type of cell death present in articular cartilage, which include the presence of some apoptotic and autophagic processes. To identify the mechanisms, as well as the chronology by which chondrocytes are eliminated during OA pathogenesis, we decided to evaluate apoptosis (by active caspase 3 and TUNEL signal) and autophagy (by LC3II molecule and cytoplasmic vacuolization) using Immunohistochemistry and Western blot techniques in an animal OA model. During OA pathogenesis, chondrocytes exhibit modifications in their death process in each zone of the cartilage. At early stages of OA, the death of chondrocytes starts with apoptosis in the superficial and part of the middle zones of the cartilage, probably as a consequence of a constant mechanical damage in the joint. As the degenerative process progresses, high incidence of active caspase 3 as well as LC3II expression are observed in the same cell, which indicate a combination of both death processes. In contrast, in the deep zone, due the abnormal subchondral bone ossification during the OA pathogenesis, apoptosis is the only mechanism observed.

Chondroptosis in Alkaptonuric Cartilage

“…This result agrees with the present tendency to emphasize the role of stress of the cell secretory machinery as an important apoptosis inductor (Ahmed et al, 2007) and suggests that Golgi and rough endoplasmic reticulum might have a key role in AKU. To the best of our knowledge, this is the first report on the occurrence of chondroptosis in AKU and the second report on the occurrence of this type of cell death after osteoarthritis (Roach et al, 2004; Pérez et al, 2005; Almonte‐Becerril et al, 2010) and one case report of traumatic injury (Sitte et al, 2009). …”

“…In the past years, a different ultra‐structural pattern for dying chondrocytes articular cartilage has been documented, displaying characteristics different from conventional apoptosis and defined as chondroptosis (Roach et al, 2004; Pérez et al, 2005; Almonte‐Becerril et al, 2010). …”

“…Although chondroptosis has some features in common with classical apoptosis and other types of cell death such as cell shrinkage, chromatin condensation and the probable involvement of caspases, other features are different such as a cytoplasmic vacuolization without nuclear fragmentation and prominent Golgi and rough endoplasmic reticulum (RER). Chondroptosis has been reported to play an important role in osteoarthritis (OA) (Roach et al, 2004; Pérez et al, 2005; Almonte‐Becerril et al, 2010; Zamli and Sharif, 2011). …”

High dose of extracellular ATP switched autophagy to apoptosis in anchorage-dependent and anchorage-independent hepatoma cells

“…When autophagy occurs, the cytoplasmic form LC3-I is processed and recruited to autophagosomes to generate LC3-II. Therefore, LC3-II is considered as a sensitive specific autophagy marker [16,17], and its expression was detected to measure the autophagy level in eATP-treated cells.…”

“…Adenosine monophosphate-activated protein kinase (AMPK) is a known physiological cellular energy sensor, which is phosphorylated at Thr172 in response to changes of cellular ATP level [17]. Activated AMPK is regarded as an efficient growth inhibitor and apoptosis inducer, even though the exact signaling transduced from AMPK has not been elucidated [18,19].…”