Induction of a program gene expression during osteoblast differentiation with strontium ranelate.
Strontium ranelate, a new agent for the treatment of osteoporosis, has been shown stimulate bone formation in various experimental models. This study examines the effect of strontium ranelate on gene expression in osteoblasts, as well as the formation of mineralized (von Kossa-positive) colony-forming unit-osteoblasts (CFU-obs). Bone marrow-derived stromal cells cultured for 21 days under differentiating conditions, when exposed to strontium ranelate, displayed a significant time- and concentration-dependent increase in the expression of the master gene, Runx2, as well as bone sialoprotein (BSP), but interestingly without effects on osteocalcin. This was associated with a significant increase in the formation of CFU-obs at day 21 of culture. In U-33 pre-osteoblastic cells, strontium ranelate significantly enhanced the expression of Runx2 and osteocalcin, but not BSP. Late, more mature osteoblastic OB-6 cells showed significant elevations in BSP and osteocalcin, but with only minimal effects on Runx2. In conclusion, strontium ranelate stimulates osteoblast differentiation, but the induction of the program of gene expression appears to be cell type-specific. The increased osteoblastic differentiation is the likely basis underlying the therapeutic bone-forming actions of strontium ranelate.
Zhu
Ling-Ling
LL
Mount Sinai Bone Program, Department of Medicine, Mount Sinai School of Medicine, New York, NY 10029, USA.
Zaidi
Samir
S
Peng
Yuanzhen
Y
Zhou
Hang
H
Moonga
Baljit S
BS
Blesius
Alexia
A
Dupin-Roger
Isabelle
I
Zaidi
Mone
M
Sun
Li
L
D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects*; D015870:Gene Expression; D051379:Mice; D008810:Mice, Inbred C57BL; D009942:Organometallic Compounds / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology*; D016133:Polymerase Chain Reaction; D013876:Thiophenes / Q000494:pharmacology*
D009942:Organometallic Compounds; D013876:Thiophenes; C081587:strontium ranelate