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Human chondrocyte apoptosis in response to mechanical injury.

Abstract：

OBJECTIVE:The effect of mechanical injury on chondrocyte viability and matrix degradation was studied. It was proposed that mechanical injury to human cartilage explants results in chondrocyte apoptosis with associated loss of glycosaminoglycans. DESIGN:Full thickness human cartilage explants, 5 mm in diameter were subjected to a single static mechanical stress of 14 MPa for 500 ms under radially unconfined compression. Glycosaminoglycan (GAG) release and percentage of cells undergoing apoptosis were measured at 96 h after injury. To establish the time course of apoptosis, explants were subjected to 30% strain and cultured for varying intervals up to 7 days after injury. A group of loaded explants were also treated with the broad spectrum caspase inhibitor z-Vad.fmk after injury. RESULTS:Internucleosomal DNA fragmentation as one indicator of apoptosis was observed in 34% (S.D.+/-11) of chondrocytes at 96 h in response to mechanical loading at 14 MPa, compared to 4% (S.D.+/-2) in the non-loaded explants. Evidence for cell death induction via apoptosis was also obtained by electron microscopy and caspase cleavage of cytokeratin. GAG release was also higher for the loaded explants, mean 1.9% (S.D.+/-0.14) of total GAG content, compared to control explants, mean 0.8% (S.D.+/-0.28). The percentage of apoptotic cells also correlated with the level of GAG release into the culture media. The percentage of apoptotic chondrocytes demonstrated a progressive increase from 6 h to 7 days post-injury. When loaded explants were cultured in z-Vad.fmk after injury, a 50% reduction in apoptosis rates was seen. CONCLUSIONS:These results demonstrate that mechanical injury induces chondrocyte apoptosis and release of GAG from the matrix. The time course suggests that a therapeutic window may exist where apoptosis could be inhibited. This potentially identifies a new approach to chondroprotection.

journal_name

Osteoarthritis Cartilage

journal_title

Osteoarthritis and cartilage

authors

D'Lima DD,Hashimoto S,Chen PC,Colwell CW Jr,Lotz MK

doi

10.1053/joca.2001.0468

keywords:

subject

Has Abstract

pub_date

2001-11-01 00:00:00

pages

712-9

issue

eissn

1063-4584

issn

1522-9653

pii

S1063-4584(01)90468-6

journal_volume

pub_type

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Human chondrocyte apoptosis in response to mechanical injury.