Effect of bisphosphonates on viability, proliferation, and dexamethasone-induced apoptosis of articular chondrocytes.
BACKGROUND
Bisphosphonates (BP) increase bone mass in patients with rheumatoid arthritis and are effective in the prevention and treatment of steroid-induced osteoporosis. However, little is known about their direct effects on chondrocytes.


OBJECTIVE
To study the influence of BP on articular chondrocytes in vitro and to investigate whether BP can prevent steroid-induced apoptosis of articular chondrocytes.


METHODS
Bovine articular chondrocytes were cultured and incubated with different concentrations of clodronate, pamidronate, risedronate, or dexamethasone. In the second part of the study, BP were added to the chondrocyte cultures one hour before co-incubation with dexamethasone. Viability and proliferation were evaluated using propidium iodide staining and tritium labelled thymidine incorporation. Apoptosis was measured with annexin V staining or the TUNEL method.


RESULTS
Only high concentrations (>10(-6) mol/l) of clodronate, pamidronate, and risedronate induced a decrease in the viability and proliferation of chondrocytes. None of the BP at concentrations ranging from 10(-12) to 10(-3) mol/l induced apoptosis. Growth retardation and apoptosis induced by dexamethasone (10(-7) mol/l) was prevented by addition of pamidronate (10(-6) mol/l) or risedronate (10(-8) or 10(-6) mol/l).


CONCLUSIONS
Bisphosphonates in therapeutic concentrations are safe for articular chondrocytes in vitro. Moreover, pamidronate and risedronate prevent dexamethasone-induced growth retardation and apoptosis of chondrocytes. These findings add evidence for a chondroprotective effect of nitrogen-containing BP, especially in patients treated with corticosteroids.
Van Offel
J F
JF
Department of Immunology, Allergology and Rheumatology, University of Antwerp, Belgium.
Schuerwegh
A J
AJ
Bridts
C H
CH
Stevens
W J
WJ
De Clerck
L S
LS
D000818:Animals; D000893:Anti-Inflammatory Agents / Q000037:antagonists & inhibitors / Q000494:pharmacology; D000963:Antimetabolites / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002358:Cartilage, Articular / Q000166:cytology / Q000187:drug effects*; D002417:Cattle; D018929:Cell Culture Techniques; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects*; D003907:Dexamethasone / Q000037:antagonists & inhibitors* / Q000494:pharmacology; D004164:Diphosphonates / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug
D000893:Anti-Inflammatory Agents; D000963:Antimetabolites; D004164:Diphosphonates; D003907:Dexamethasone