TY - JOUR
T1 - Intercellular signalling as a cause of cell death in cyclically impacted cartilage explants
AU - Levine, A.
AU - Burton-Wurster, N.
AU - Chen, C. T.
AU - Lust, G.
N1 - Funding Information:
The authors wish to thank Alma Williams for technical assistance, Dr Barbara Butcher for instruction in confocal microscopy, Dr Stephen E. Bloom for sharing his expertise in the study of apoptosis, and Dorothy Scorelle for secretarial assistance. The authors acknowledge the financial support from NIH grants AR35664 and AR47558.
PY - 2001/11
Y1 - 2001/11
N2 - Recently, in vitro cartilage studies have shown that impact loading can produce structural damage and osteoarthritis-like changes, including tissue swelling, collagen denaturation, and cell death. Objective: This study was to determine whether a signal for cell death moves through the cartilage matrix, resulting in the spread of cell death over time from impacted to unimpacted regions. Design: Cyclic impacts were applied to the 2 mm core of 4 mm cartilage discs. Post-impact culturing extended for 3, 6 or 21 days and occurred in one of two ways. In one, discs were cultured intact. In the second, cores were removed immediately after cessation of impact and cores and rings cultured separately. Cells in apoptosis and later stage necrosis were monitored using the TUNEL assay. Results: The extent of cell death in impacted samples increased with increased duration of post-impact culturing. At the early time, the majority of cell death was located in the regions of direct impact whereas after extended culture, the extent of cell death was similar in the surrounding unimpacted regions and in the impacted core region. However, the physical separation of the impacted core from the surrounding, non-impacted ring regions immediately after impact, and prior to independent culture, kept the level of cell death in the surrounding ring close to control levels, even after 21 days of incubation. Discussion: These findings indicate that soluble intercellular signalling is involved in the spreading of cell death through the cartilage matrix, and that its effects can be prevented by physical isolation of the surrounding ring from the impacted core.
AB - Recently, in vitro cartilage studies have shown that impact loading can produce structural damage and osteoarthritis-like changes, including tissue swelling, collagen denaturation, and cell death. Objective: This study was to determine whether a signal for cell death moves through the cartilage matrix, resulting in the spread of cell death over time from impacted to unimpacted regions. Design: Cyclic impacts were applied to the 2 mm core of 4 mm cartilage discs. Post-impact culturing extended for 3, 6 or 21 days and occurred in one of two ways. In one, discs were cultured intact. In the second, cores were removed immediately after cessation of impact and cores and rings cultured separately. Cells in apoptosis and later stage necrosis were monitored using the TUNEL assay. Results: The extent of cell death in impacted samples increased with increased duration of post-impact culturing. At the early time, the majority of cell death was located in the regions of direct impact whereas after extended culture, the extent of cell death was similar in the surrounding unimpacted regions and in the impacted core region. However, the physical separation of the impacted core from the surrounding, non-impacted ring regions immediately after impact, and prior to independent culture, kept the level of cell death in the surrounding ring close to control levels, even after 21 days of incubation. Discussion: These findings indicate that soluble intercellular signalling is involved in the spreading of cell death through the cartilage matrix, and that its effects can be prevented by physical isolation of the surrounding ring from the impacted core.
KW - Apoptosis
KW - Cartilage
KW - Mechanical damage
KW - Osteoarthritis
UR - http://www.scopus.com/inward/record.url?scp=0034746842&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=0034746842&partnerID=8YFLogxK
U2 - 10.1053/joca.2001.0467
DO - 10.1053/joca.2001.0467
M3 - Article
C2 - 11795989
AN - SCOPUS:0034746842
SN - 1063-4584
VL - 9
SP - 702
EP - 711
JO - Osteoarthritis and Cartilage
JF - Osteoarthritis and Cartilage
IS - 8
ER -