Tigogenin inhibits adipocytic differentiation and induces osteoblastic differentiation in mouse bone marrow stromal cells.
We investigated the effect of tigogenin on adipocytic and osteoblastic differentiation in mouse bone marrow stromal cells (BMSCs). Tigogenin enhanced the proliferation of BMSCs significantly. Tigogenin treatment reduced the adipogenic induction of lipid accumulation, visfatin secretion, and the expressions of peroxisome proliferation-activated receptor (PPAR)gamma2 and adipocyte fatty acid-binding protein (ap)2. Moreover, tigogenin had no effect on the mitotic clonal expansion. On the other hand, tigogenin significantly elevated alkaline phosphatase (ALP) activity and the expressions of Cbfa1, collagen type I (COL I) and osteocalcin (OCN), as well as the content of matrix calcium in BMSCs. Further, SB-203580 antagonized the tigogenin-promoted osteogenesis. These observations suggested that tigogenin may modulate differentiation of BMSCs to cause a lineage shift away from the adipocytes and toward the osteoblasts, which is at least mediated by inhibition of PPARgamma and via p38 MAPK pathway, and is a potential drug preventing the development of osteoporosis and the related disorders.
Zhou
Hua
H
Life Science Division, Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, PR China.
Yang
Xi
X
Wang
Naili
N
Zhang
Yaou
Y
Cai
Guoping
G
D017667:Adipocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D000469:Alkaline Phosphatase / Q000378:metabolism; D000818:Animals; D001854:Bone Marrow Cells / Q000166:cytology* / Q000187:drug effects / Q000201:enzymology; D002454:Cell Differentiation / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002999:Clone Cells; D016207:Cytokines / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors; D008938:Mitosis / Q000187:drug effects; D054409:Nicotinamide Phosphoribosyltransferase; D010006:Osteoblasts / Q000166:cytology* / Q000187:drug effects; D015675:Osteocalcin / Q000235:genetics / Q000378:metabolism; D010012:Osteogenesis / Q000187:drug effects; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D013150:Spirostans / Q000494:pharmacology*; D017154:Stromal Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D050656:Transcription Factor AP-2 / Q000235:genetics / Q000378:metabolism
D016207:Cytokines; D004791:Enzyme Inhibitors; D047495:PPAR gamma; D013150:Spirostans; D050656:Transcription Factor AP-2; D015675:Osteocalcin; C046297:sarsasapogenin; D054409:Nicotinamide Phosphoribosyltransferase; C495867:nicotinamide phosphoribosyltransferase, mouse; D020928:Mitogen-Activated Protein Kinases; D000469:Alkaline Phosphatase