Effects of potassium and anion channel blockers on the cellular response of human osteoarthritic chondrocytes.
The aim of this article is to determine to what extent the proliferation, CD44 expression, and apoptosis behavior of cells can be influenced by the modulation of ion channel activity on the cell membrane of human osteoarthritic chondrocytes. The potassium channel blocker 4-aminopyridine (4-AP) and the chloride and anion channel blocker 4-acetamido-4'-isothiocyano-2,2'-disulfonic acid stilbene (SITS) were used as ion channel modulators. Assessment of the proliferation was done by incorporation of (3)H-thymidine. The detection of apoptotic cells and expression of the hyaluronic acid binding CD44-receptor were determined by flow cytometry. The results showed that 4-AP and SITS lead to a temporary increase in (3)H-thymidine incorporation, followed by a suppression of proliferation after a 12-day incubation. 4-AP causes considerable cytotoxic effects. SITS leads to necrotic cell damage. CD44 expression is increased up to 43% after incubation with 4-AP for 24 or 48 h, whereas prolonged incubation under SITS influence leads to a clear inhibition of CD44 expression. In conclusion, proliferation, CD44 expression, and apoptosis behavior of human chondrocytes can be influenced by modulation of ion channel activity. These results serve as a basis for further investigations to extend the therapeutic possibilities in the treatment of arthritis.
Department of Orthopedics, Martin Luther University Halle Wittenberg, 06097 Halle, Germany.
David
D
Wohlrab
Michaela
M
Vocke
Thomas
T
Klapperstück
Werner
W
Hein
D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid / Q000494:pharmacology*; D015761:4-Aminopyridine / Q000494:pharmacology*; D000368:Aged; D017209:Apoptosis / Q000187:drug effects; D001168:Arthritis / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D019902:Chondrocytes / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D005260:Female; D006801:Humans; D018960:Hyaluronan Receptors / Q000096:biosynthesis; D007473:Ion Channels / Q000037:antagonists & inhibitors*; D008297:Male; D008875:Middle Aged; D026902:Potassium Channel Blockers / Q000494:pharmacology*
D018960:Hyaluronan Receptors; D007473:Ion Channels; D026902:Potassium Channel Blockers; D012856:4-Acetamido-4'-isothiocyanatostilbene-2,2'-disulfonic Acid; D015761:4-Aminopyridine