Effect of 1 alpha,25(OH)(2)-vitamin D-3 on TNF alpha-mediated apoptosis ofhuman primary osteoblast-like cells in vitro

1 alpha,25(OH)(2)-vitamin D-3 is a hormone which potentially stimulates bon e cell growth and differentiation. TNF alpha: is one possible inductor for apoptosis; apoptosis being an important regulatoring factor for bone modell ing and remodelling. We examined the influence of physiological levels (0.1 nM) 1 alpha,25(OH)(2)-vitamin D-3 on TNF alpha-mediated apoptosis in human osteoblast-like cells. These human cells were obtained from bone fragments obtained during orthopedic operations on patients without systemic bone dis ease. Treatment with 1 alpha,25(OH)(2)-vitamin D-3 for 8 weeks resulted in a significant reduction (30%) of viable cell number compared to untreated c ells. Incubation with TNF alpha (100 ng/ml for 4 hours) only had limited ef fects on the rate of apoptosis in control cells. After pretreatment with 1 alpha,25(OH)(2)-vitamin D-3, induction of apoptosis increased up to 10% in human osteoblast-like cells. In parallel to the induction of apoptosis, 1 a lpha,25(OH)(2)-vitamin D-3 stimulated osteocalcin and alkaline phosphatase as markers of mature osteoblasts. Our data suggest that 1 alpha,25(OH)(2)-v itamin D-3 has a stimulatory effect on TNF alpha-induced apoptosis in human osteoblast-like cells as a result of 1 alpha,25(OH)(2)-vitamin D-3-induced cell differentiation.