Beneficial effects of intra-articular caspase inhibition therapy following osteochondral injury

Dang, Alexis; Warren, A.P.; Kim, H.T.

doi:10.1016/j.joca.2005.12.010

Cited by 34 publications

(31 citation statements)

References 24 publications

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“…Furthermore, shear strain is exaggerated in degenerative cartilage samples (32). Also of interest are reports that administering pancaspase inhibitors to experimental OA models resulted in fewer cartilage lesions by preventing cell death (8,36).…”

Section: Discussionmentioning

confidence: 99%

Role of lubricin and boundary lubrication in the prevention of chondrocyte apoptosis

Waller

Zhang

Elsaid

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

217

179

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Osteoarthritis is a complex disease involving the mechanical breakdown of articular cartilage in the presence of altered joint mechanics and chondrocyte death, but the connection between these factors is not well established. Lubricin, a mucinous glycoprotein encoded by the PRG4 gene, provides boundary lubrication in articular joints. Joint friction is elevated and accompanied by accelerated cartilage damage in humans and mice that have genetic deficiency of lubricin. Here, we investigated the relationship between coefficient of friction and chondrocyte death using ex vivo and in vitro measurements of friction and apoptosis. We observed increases in whole-joint friction and cellular apoptosis in lubricin knockout mice compared with wild-type mice. When we used an in vitro bovine explant cartilage-on-cartilage bearing system, we observed a direct correlation between coefficient of friction and chondrocyte apoptosis in the superficial layers of cartilage. In the bovine explant system, the addition of lubricin as a test lubricant significantly lowered the static coefficient of friction and number of apoptotic chondrocytes. These results demonstrate a direct connection between lubricin, boundary lubrication, and cell survival and suggest that supplementation of synovial fluid with lubricin may be an effective treatment to prevent cartilage deterioration in patients with genetic or acquired deficiency of lubricin.camptodactyly-arthropathy-coxa vara-pericarditis | shear strain | antiadhesion | tribology

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Section: Discussionmentioning

confidence: 99%

Role of lubricin and boundary lubrication in the prevention of chondrocyte apoptosis

Waller

Zhang

Elsaid

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

217

179

View full text Add to dashboard Cite

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“…9,12,13 Interestingly, recent studies have shown that short-term intra-articular administration of a potent caspase inhibitor (Z-VAD-FMK, ZVF) results in a decrease in chondrocyte apoptosis and subsequently less cartilage degeneration after experimental osteochondral injury in rabbits. 14 Further, the use of apoptosis inhibitors in vivo reduced the number of cells undergoing apoptosis in cartilage that had been prepared for surgery, leading to the conclusions that cell death inhibitors could improve the results of cartilage repair surgery. 15 In the light of these findings, we hypothesized that inhibition of the cell death that occurs as a response to wounding of articular cartilage will result in enhanced cartilage integrative repair.…”

Section: Introductionmentioning

confidence: 99%

Enhanced Tissue Integration During Cartilage Repair In Vitro Can Be Achieved by Inhibiting Chondrocyte Death at the Wound Edge

Gilbert

Singhrao

Khan

et al. 2009

Tissue Engineering Part A

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“…While the benefits of apoptosis inhibition have been demonstrated in animal models of degenerative arthritis, cartilage injury, and cartilage repair using marrow-stimulation techniques [13,17,40], the in vivo effects of apoptosis inhibition in the setting of osteochondral allograft transplantation have not been reported. Based upon existing research, beneficial effects would be anticipated.…”

Section: Discussionmentioning

confidence: 99%

“…Although a variety of different stimuli initiate chondrocyte apoptosis [2,3,6,9,10,23,24,26,30,32], a universal feature of chondrocyte apoptosis is caspase activation [13,16,17,31,35,39,44] (Fig. 1).…”

Section: Chondrocyte Apoptosis Regulation Pathwaysmentioning

confidence: 99%

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Chondrocyte Apoptosis: Implications for Osteochondral Allograft Transplantation

Kim

Teng

Dang

2008

Clin Orthop Relat Res

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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.

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Beneficial effects of intra-articular caspase inhibition therapy following osteochondral injury

Cited by 34 publications

References 24 publications

Role of lubricin and boundary lubrication in the prevention of chondrocyte apoptosis

Role of lubricin and boundary lubrication in the prevention of chondrocyte apoptosis

Enhanced Tissue Integration During Cartilage Repair In Vitro Can Be Achieved by Inhibiting Chondrocyte Death at the Wound Edge

Chondrocyte Apoptosis: Implications for Osteochondral Allograft Transplantation

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