Effects of 1alpha,25-dihydroxyvitamin D3 and growth hormone on apoptosis and proliferation in UMR 106 osteoblast-like cells.
Mechanisms maintaining a correct balance between bone-forming osteoblasts and bone-resorbing osteoclasts are essential for bone formation. Apoptosis has been proposed to play a key role in controlling osteoblast homeostasis. 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] and GH, which are important regulators of bone growth and bone metabolism, also play pivotal roles in regulation of mitogenesis, differentiation, and apoptosis. We have recently shown that 1,25(OH)2D3 prolongs GH signaling via the Janus kinase 2 (JAK2)/STAT5 (signal transducer and activator of transcription 5) pathway in UMR 106 osteoblast-like cells. In the present study, we have investigated the effects of GH and 1,25(OH)2D3 on proliferation and apoptosis in UMR 106 cells. We found that 1,25(OH)2D3 and GH, separate or in combination, inhibited apoptosis. GH also had profound effects on cell cycle distribution and proliferation. In addition, pretreatment of cells with 1,25(OH)2D3 was necessary to detect GH-induced MAPK activation. We hypothesize that these hormones separately regulate the processes of apoptosis and proliferation, which may be important for maintaining osteoblast cell number.
Morales
Orlando
O
Center for Surgical Sciences, Department of Medical Nutrition, Karolinska Institutet, Huddinge, Sweden.
Samuelsson
Magnus K R
MK
Lindgren
Urban
U
Haldosén
Lars-Arne
LA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001859:Bone Neoplasms; D002117:Calcitriol / Q000494:pharmacology*; D002120:Calcium Channel Agonists / Q000494:pharmacology*; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases / Q000378:metabolism; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D013006:Growth Hormone / Q000494:pharmacology; D020935:MAP Kinase Signaling System / Q000187:drug effects; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects* / Q000201:enzymology; D012516:Osteosarcoma; D051381:Rats
D002120:Calcium Channel Agonists; D013006:Growth Hormone; C505410:Casp3 protein, rat; C505528:Casp8 protein, rat; C506435:Casp9 protein, rat; D053148:Caspase 3; D053181:Caspase 8; D053453:Caspase 9; D020169:Caspases; D002117:Calcitriol