FK506 enhanced osteoblastic differentiation in mesenchymal cells.
Bone morphogenetic protein (BMP) is a bone-derived growth factor capable of promoting the differentiation of mesenchymal cells into osteogenic lineage pathways. Recently, immunosuppressants were reported to cause a moderate increase in osteoblastic differentiation in a rat osteoblast-like osteosarcoma cell line. If immunosuppressants can induce osteoblastic differentiation, it will be useful for bone tissue transplantation. We assessed the effect of immunosuppressants with or without BMP-4 on inducing osteoblastic differentiation in osteoblast-like and other mesenchymal cells. FK506, an immunosuppressant often used clinically, induced a dose- and time-dependent increase in alkaline phosphatase (ALP) activity, one of the markers of osteoblast differentiation, in cells derived from mesenchyma. In the presence of BMP-4, ALP activity, mRNA levels of ALP and osteocalcin increased. FK506 was found to not only stimulate osteoblastic differentiation, but also to enhance BMP-4 induced osteoblastic differentiation. These results suggest that FK506 promotes differentiation of osteoblastic cells.
Tang
Lin
L
Department of Orthopaedic Surgery, Shinshu University School of Medicine, 3-1-1 Asahi, Matsumoto, 390-8621, Japan. soebara@hsp.md.shinshu-u.ac.jp
Ebara
Sohei
S
Kawasaki
Satoshi
S
Wakabayashi
Shinji
S
Nikaido
Toshio
T
Takaoka
Kunio
K
D016475:3T3 Cells; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D015152:Blotting, Northern; D001854:Bone Marrow Cells / Q000378:metabolism; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D002454:Cell Differentiation; D002455:Cell Division; D002460:Cell Line; D002478:Cells, Cultured; D017077:Culture Media, Conditioned / Q000494:pharmacology; D016572:Cyclosporine / Q000494:pharmacology; D018076:DNA, Complementary / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D007166:Immunosuppressive Agents / Q000494:pharmacology*; D008648:Mesoderm / Q000166:cytology*; D051379:Mice; D008809:Mice, Inbred C3H; D010006:Osteoblasts / Q000378:metabolism*; D015675:Osteocalcin / Q000378:metabolism; D012516:Osteosarcoma / Q000378:metabolism; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D020133:Reverse Transcriptase Polymerase Chain Reaction; D020123:Sirolimus / Q000494:pharmacology; D016559:Tacrolimus / Q000494:pharmacology*; D013997:Time Factors
C525810:Bmp4 protein, mouse; C525811:Bmp4 protein, rat; D055415:Bone Morphogenetic Protein 4; D019485:Bone Morphogenetic Proteins; D017077:Culture Media, Conditioned; D018076:DNA, Complementary; D007166:Immunosuppressive Agents; D012333:RNA, Messenger; D015675:Osteocalcin; D016572:Cyclosporine; D000469:Alkaline Phosphatase; D020123:Sirolimus; D016559:Tacrolimus