Chondrocyte Apoptosis: Implications for Osteochondral Allograft Transplantation

Abstract

Osteochondral allograft transplantation is a useful technique to manage larger articular cartilage injuries. One factor that may compromise the effectiveness of this procedure is chondrocyte cell death that occurs during the storage, preparation, and implantation of the osteochondral grafts. Loss of viable chondrocytes may negatively affect osteochondral edge integration and longterm function. A better understanding of the mechanisms responsible for chondrocyte loss could lead to interventions designed to decrease cell death and improve results. Recent studies indicate that apoptosis, or programmed cell death, is responsible for much of the chondrocyte death associated with osteochondral allograft transplantation. Theoretically, some of these cells can be rescued by blocking important apoptotic mediators. We review the role of apoptosis in cartilage degeneration, focusing on apoptosis associated with osteochondral transplantation. We also review the pathways thought to be responsible for regulating chondrocyte apoptosis, as well as experiments testing inhibitors of the apoptotic pathway. These data suggest that key contributors to the apoptotic process can be manipulated to enhance chondrocyte survival. This knowledge may lead to better surgical outcomes for osteochondral transplantation.

RNA‐seq analysis of clinical‐grade osteochondral allografts reveals activation of early response genes

“…Although many factors can initiate chondrocyte apoptosis, activation of cysteinyl aspartate‐specific proteases (Caspases) is a major downstream enzymatic pathway that mediates programmed cell death . Indeed, broad‐spectrum caspase inhibitors block apoptosis and enhance the survival of bovine osteochondral allograft chondrocytes during storage . Our study reveals the mechanistic underpinning of this latter finding by showing upregulation of genes associated with apoptosis in stored allografts.…”

Reengineering autologous bone grafts with the stem cell activator WNT3A

“…For example, even when freshly harvested BGM is maintained at room temperature there is significant cellular apoptosis [38,74,75]. In an effort to create a more effective biomaterial, we treated autografts with L-WNT3A and found that compared to control (untreated) BGM, BGM WNT exhibits~50% fewer TUNEL-positive cells [38].…”

Experimental research Assessment of apoptosis and MMP-1, MMP-3 and TIMP-2 expression in tibial hyaline cartilage after viable medial meniscus transplantation in the rabbit

“…The lack of apoptosis in the control group proves that sole knee joint arthrotomy does not influence the induction of hyaline cartilage chondrocyte apoptosis. Apoptosis is rarely detected in normal native cartilage [15, 29]. …”

“…Apoptosis – a highly regulated and controlled process of cell death – participates in homeostasis by eliminating wasted or mutated cells [15, 16, 19, 20]. Metalloproteinases, zinc-dependent endopeptidases, on the other hand participate in cellular matrix transformations, providing the equilibrium between production and degradation of the extracellular matrix [17, 18].…”