Osteoblastic differentiation is enhanced by rapamycin in rat osteoblast-like osteosarcoma (ROS 17/2.8) cells.
The effects of three immunosuppressants (rapamycin, FK506 and cyclosporin A) on the proliferation and differentiation of rat osteoblasts-like osteosarcoma cell line, ROS 17/2.8 (ROS) cells were examined in vitro. All immunosuppressants showed a direct inhibition on the proliferation of ROS cells with different potencies. Growth inhibition by rapamycin was stronger than that by FK506 or cyclosporin A. Rapamycin caused a significant increase in alkaline phosphatase (ALP) activity and in the expression of osteopontin and osteocalcin mRNAs. FK506 caused a moderate increase in ALP activity and a decreased expression of osteopontin mRNA. Cyclosporin A caused a decrease in ALP activity and in the expression of type 1 alpha 1 collagen mRNA. Our study indicates that rapamycin directly acts on ROS cells and induces osteoblastic differentiation, however, the effect of FK506 and cyclosporin A is weak. Rapamycin significantly enhances the differentiation induced by 1,25(OH)2-vitaminD3.
Department of Maxillofacial Surgery, Faculty of Medicine, Kagawa Medical University, Japan.
T
T
Ogawa
M
M
Tokuda
K
K
Tomizawa
H
H
Matsui
T
T
Itano
R
R
Konishi
S
S
Nagahata
O
O
Hatase
D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002117:Calcitriol / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D010006:Osteoblasts / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D015675:Osteocalcin / Q000096:biosynthesis; D053495:Osteopontin; D012516:Osteosarcoma / Q000473:pathology*; D011090:Polyenes / Q000494:pharmacology*; D051381:Rats; D012795:Sialoglycoproteins / Q000096:biosynthesis; D020123:Sirolimus; D016559:Tacrolimus / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000903:Antibiotics, Antineoplastic; D007166:Immunosuppressive Agents; D011090:Polyenes; D012795:Sialoglycoproteins; C506897:Spp1 protein, rat; D015675:Osteocalcin; D053495:Osteopontin; D016572:Cyclosporine; D002117:Calcitriol; D020123:Sirolimus; D016559:Tacrolimus