Effect of 1alpha,25(OH)2-vitamin D3 on TNF alpha-mediated apoptosis of human primary osteoblast-like cells in vitro.
1alpha,25(OH)2-vitamin D3 is a hormone which potentially stimulates bone cell growth and differentiation. TNFalpha is one possible inductor for apoptosis; apoptosis being an important regulatoring factor for bone modelling and remodelling. We examined the influence of physiological levels (0.1 nM) 1alpha,25(OH)2-vitamin D3 on TNFalpha-mediated apoptosis in human osteoblast-like cells. These human cells were obtained from bone fragments obtained during orthopedic operations on patients without systemic bone disease. Treatment with 1alpha,25(OH)2-vitamin D3 for 8 weeks resulted in a significant reduction (30%) of viable cell number compared to untreated cells. Incubation with TNFalpha (100 ng/ml for 4 hours) only had limited effects on the rate of apoptosis in control cells. After pretreatment with 1alpha,25(OH)2-vitamin D3, induction of apoptosis increased up to 10% in human osteoblast-like cells. In parallel to the induction of apoptosis, 1alpha,25(OH)2-vitamin D3 stimulated osteocalcin and alkaline phosphatase as markers of mature osteoblasts. Our data suggest that 1alpha,25(OH)2-vitamin D3 has a stimulatory effect on TNFalpha-induced apoptosis in human osteoblast-like cells as a result of 1alpha,25(OH)2-vitamin D3-induced cell differentiation.
Pascher
E
E
Department of Endocrinology, Heinrich-Heine University of Düsseldorf, Germany. pascher@uni-duesseldorf.de
Perniok
A
A
Becker
A
A
Feldkamp
J
J
D000469:Alkaline Phosphatase / Q000032:analysis; D017209:Apoptosis / Q000187:drug effects*; D002117:Calcitriol / Q000494:pharmacology*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D002478:Cells, Cultured; D005434:Flow Cytometry; D006801:Humans; D010006:Osteoblasts / Q000166:cytology* / Q000201:enzymology / Q000378:metabolism; D015675:Osteocalcin / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D002120:Calcium Channel Agonists; D014409:Tumor Necrosis Factor-alpha; D015675:Osteocalcin; D000469:Alkaline Phosphatase; D002117:Calcitriol