Enhanced tissue integration during cartilage repair in vitro can be achieved by inhibiting chondrocyte death at the wound edge.

Abstract

OBJECTIVE:

Experimental wounding of articular cartilage results in cell death at the lesion edge. The objective of this study was to investigate whether inhibition of this cell death results in enhanced integrative cartilage repair.

METHODS:

Bovine articular cartilage discs (6 mm) were incubated in media containing inhibitors of necrosis (Necrostatin-1, Nec-1) or apoptosis (Z-VAD-FMK, ZVF) before cutting a 3 mm inner core. This core was left in situ to create disc/ring composites, cultured for up to 6 weeks with the inhibitors, and analyzed for cell death, sulfated glycosaminoglycan release, and tissue integration.

RESULTS:

Creating the disc/ring composites resulted in a significant increase in necrosis. ZVF significantly reduced necrosis and apoptosis at the wound edge. Nec-1 reduced necrosis. Both inhibitors reduced the level of wound-induced sulfated glycosaminoglycan loss. Toluidine blue staining and electron microscopy of cartilage revealed significant integration of the wound edges in disc/ring composites treated with ZVF. Nec-1 improved integration, but to a lesser extent. Push-out testing revealed that ZVF increased adhesive strength compared to control composites.

CONCLUSIONS:

This study shows that treatment of articular cartilage with cell death inhibitors during wound repair increases the number of viable cells at the wound edge, prevents matrix loss, and results in a significant improvement in cartilage-cartilage integration.

• Authors: Sophie J Gilbert, Sim K Singhrao, Ilyas M Khan, Lee G Gonzalez, Brian M Thomson, Drew Burdon, Victor C Duance, Charles W Archer
• Journal: Tissue engineering. Part A (Tissue Eng Part A) Vol. 15 Issue 7 Pg. 1739-49 (Jul 2009) ISSN: 1937-335X [Electronic] United States
• PMID: 19119922 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Amino Acid Chloromethyl Ketones
• Caspase Inhibitors
• Collagen Type II
• Enzyme Inhibitors
• Imidazoles
• Indoles
• Proteoglycans
• benzyloxycarbonylvalyl-alanyl-aspartyl fluoromethyl ketone
• necrostatin-1

Topics

• Amino Acid Chloromethyl Ketones (pharmacology)
• Animals
• Cartilage (drug effects, enzymology, pathology, ultrastructure)
• Caspase Inhibitors
• Cattle
• Cell Death (drug effects)
• Chondrocytes (drug effects, pathology)
• Collagen Type II (genetics, metabolism)
• Enzyme Inhibitors (pharmacology)
• Extracellular Matrix (drug effects, metabolism)
• Gene Expression Regulation (drug effects)
• Imidazoles (pharmacology)
• Immunohistochemistry
• Indoles (pharmacology)
• Materials Testing
• Mechanical Phenomena (drug effects)
• Proteoglycans (metabolism)
• Tissue Engineering
• Wound Healing (drug effects)