Proteome Alterations in Equine Osteochondrotic Chondrocytes

Abstract

Osteochondrosis is a failure of the endochondral ossification that affects developing joints in humans and several animal species. It is a localized idiopathic joint disorder characterized by focal chondronecrosis and growing cartilage retention, which can lead to the formation of fissures, subchondral bone cysts, or intra-articular fragments. Osteochondrosis is a complex multifactorial disease associated with extracellular matrix alterations and failure in chondrocyte differentiation, mainly due to genetic, biochemical, and nutritional factors, as well as traumas. This study describes the main proteomic alterations occurring in chondrocytes isolated from osteochondrotic cartilage fragments. A comparative analysis performed on equine osteochondrotic and healthy chondrocytes showed 26 protein species as differentially represented. In particular, quantitative changes in the extracellular matrix, cytoskeletal and chaperone proteins, and in cell adhesion and signaling molecules were observed in osteochondrotic cells, compared to healthy controls. Functional group analysis annotated most of these proteins in “growth plate and cartilage development”, while others were included in “glycolysis and gluconeogenesis”, “positive regulation of protein import”, “cell–cell adhesion mediator activity”, and “mitochondrion nucleoid”. These results may help to clarify some chondrocyte functional alterations that may play a significant role in determining the onset and progression of equine osteochondrosis and, being related, of human juvenile osteochondrosis.

Comparative label-free proteomic analysis of equine osteochondrotic chondrocytes

“…In accordance with our previous study [24], changes in the abundance of cytoskeletal proteins were detected. In addition to the high levels of actin, herein alterations were observed in abundance of proteins included in cytoskeletal structures such as "actin filament" and "stress fiber".…”

“…Moreover, the results confirmed the role of nutrition in OC pathogenesis and highlighted a probable involvement of lysosomal enzymes. According to previous studies [24,25] the deregulation of proteins involved in endoplasmic reticulum stress response and protein folding and localization were also observed.…”

“…Several proteomic studies have already been carried out to improve the understanding of the physiopathology of joint diseases such as OA, rheumatoid arthritis (RA) and juvenile idiopathic arthritis [16][17][18][19][20][21][22], however few studies have focused on the proteomic analysis of OC [23][24][25][26][27][28]. Chondrocytes are the unique cartilage cell type and therefore playing an important role in bone growth and elongation and promote ECM remodelling and replacement.…”

“…Chondrocytes are the unique cartilage cell type and therefore playing an important role in bone growth and elongation and promote ECM remodelling and replacement. However, the only proteomic study on OC chondrocytes was performed using a two-dimensional electrophoresis (2DE)-based approach [24].…”

Molecular Processes in Chondrocyte Biology

“…Elisabetta Chiaradia and colleagues performed a proteome analysis of equine osteochondrosis, which is a joint disorder characterized by focal chondronecrosis and growing cartilage retention. The extracellular matrix, cytoskeletal, chaperone, cell adhesion, and signaling proteins were differentially expressed in chondrocytes from osteochondrotic cartilage compared with those from healthy cartilage [14]. Eriko Toyada and colleagues examined the efficiency of polydactyly-derived chondrocyte sheets using an orthotopic xenogeneic transplantation model, and the efficacy-correlated genes and proteins were identified by transcriptomic and proteomic analyses.…”