Agents that block fibronectin fragment-mediated cartilage damage also promote repair.
OBJECTIVE
The objective was to determine if agents that suppress catabolism might also enhance repair of irreversibly damaged cartilage.


METHODS
Articular cartilage from bovine metacarpophalangeal joints was studied in explant culture.


METHODS
Fibronectin fragments or IL-1 alpha, which potently cause proteoglycan (PG) loss from cartilage, were added to cultures also containing the catabolism-blocking agents: insulin-like growth factor-1, or N-acetylcysteine, or Arg-Gly-Asp-Ser peptide, and the effects of these agents on blocking PG loss determined. To test for repair or restoration of PG, cartilage was first damaged, damage agents removed and inhibitory agents added.


METHODS
Each mean and SD value for cartilage PG content was determined by assays of papain digests of cartilage from three similar cultures.


RESULTS
The agents either partially or fully blocked PG loss and promoted repair.


CONCLUSIONS
Normally irreversible cartilage damage was reversed by slowing ongoing catabolic processes during attempted repair. Thus, catabolic inhibitors have reparative potential.
Homandberg
G A
GA
Department of Biochemistry, Rush Medical College, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL 60612-3864, USA. ghomandb@rush.edu
Wen
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Hui
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D000111:Acetylcysteine / Q000494:pharmacology; D000818:Animals; D002358:Cartilage, Articular / Q000187:drug effects* / Q000473:pathology; D002417:Cattle; D005353:Fibronectins / Q000037:antagonists & inhibitors / Q000633:toxicity*; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007375:Interleukin-1 / Q000037:antagonists & inhibitors / Q000633:toxicity*; D008662:Metacarpophalangeal Joint; D009842:Oligopeptides / Q000494:pharmacology; D010446:Peptide Fragments / Q000633:toxicity*; D011509:Proteoglycans / Q000378:metabolism*
D005353:Fibronectins; D007375:Interleukin-1; D009842:Oligopeptides; D010446:Peptide Fragments; D011509:Proteoglycans; D007334:Insulin-Like Growth Factor I; C046617:arginyl-glycyl-aspartyl-serine; D000111:Acetylcysteine