The divalent strontium salt S12911 enhances bone cell replication and bone formation in vitro.
In this study, we have determined the effect of the divalent strontium salt S12911 on bone cell replication and bone formation in two culture systems. In the first series of experiments, half-calvariae of newborn rats were cultured with S12911 from 24 to 96 h and labeled with 3H-thymidine for the last 6 h of culture or treated with S12911 for 24 h and labeled for 24 h with 3H-proline 24-48 h after the removal of the agent. Calvariae were then processed for histomorphometry. S12911 at 10(-3) M increased the replication of preosteoblastic cells by 30-50% after 24 h and by 60% after 96 h of treatment. This effect was specific, since the number of labeled osteoblasts and of periosteal cells was not changed. A transient 24 h treatment with S12911 at 10(-3) M increased bone formation 24 and 48 h after the removal of the agent. 3H-proline labeled surfaces and bone formation rates were increased by 20%-35%. In the second series of experiments, sequential collagenase digestions were used to isolate cell populations enriched in fibroblasts or osteoblasts (Ob) from 22 day fetal rat calvariae. Treatment with S12911 at 10(-3) M for 24 h enhanced DNA synthesis by three- to fourfold in cell populations enriched in fibroblasts and preosteoblastic cells. The effect was less pronounced and inconsistent in Ob cells. S12911 at 10(-3) M for 24 h also increased collagen and non-collagen protein synthesis by 35% in Ob cells. These data indicate that the divalent strontium salt S12911 enhances bone cell replication and bone formation in vitro, an effect that may contribute to the previously reported effects of S12911 on trabecular bone mass in vivo.
Canalis
E
E
Saint Francis Hospital and Medical Center, Department of Research, Hartford, CT 06105-1299, USA.
Hott
M
M
Deloffre
P
P
Tsouderos
Y
Y
Marie
P J
PJ
D000818:Animals; D000831:Animals, Newborn; D015519:Bone Density / Q000187:drug effects; D001846:Bone Development / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D003094:Collagen / Q000096:biosynthesis; D005347:Fibroblasts / Q000166:cytology / Q000187:drug effects*; D007553:Isotope Labeling; D009942:Organometallic Compounds / Q000494:pharmacology*; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects; D013876:Thiophenes / Q000494:pharmacology*; D013936:Thymidine / Q000378:metabolism; D014475:Uncoupling Agents / Q000494:pharmacology*
D009942:Organometallic Compounds; D013876:Thiophenes; D014475:Uncoupling Agents; C081587:strontium ranelate; D003094:Collagen; D013936:Thymidine