Anabolic activity of ursolic acid in bone: Stimulating osteoblast differentiation in vitro and inducing new bone formation in vivo.
In the field of osteoporosis, there has been growing interest in anabolic agents that enhance bone mass and improve bone architecture. In this study, we demonstrated that the ubiquitous plant triterpenoid, ursolic acid, enhances differentiation and mineralization of osteoblasts in vitro. We found that ursolic acid induced the expression of osteoblast-specific genes with the activation of mitogen-activated protein kinases, nuclear factor-kappaB, and activator protein-1. Additionally, noggin, an antagonist of bone morphogenetic proteins (BMPs), inhibited ursolic acid-induced osteoblast differentiation. Noggin also inhibited the activation of Smad and the induction of BMP-2 mRNA expression by ursolic acid in the late stage of osteoblast differentiation. Importantly, ursolic acid was shown to have bone-forming activity in vivo in a mouse calvarial bone formation model. A high proportion of positive immunostaining of BMP-2 was found in the nuclear region of woven bone formed by ursolic acid. These results suggested that ursolic acid has the anabolic potential to stimulate osteoblast differentiation and enhance new bone formation.
Lee
Su-Ui
SU
Laboratory of Chemical Genomics, Korea Research Institute of Chemical Technology, P.O. Box 107, Yuseong-gu, Daejeon 305-600, Republic of Korea.
Park
Sang-Joon
SJ
Kwak
Han Bok
HB
Oh
Jaemin
J
Min
Yong Ki
YK
Kim
Seong Hwan
SH
D000469:Alkaline Phosphatase / Q000235:genetics / Q000378:metabolism; D045930:Anabolic Agents; D000818:Animals; D000880:Anthraquinones; D015153:Blotting, Western; D001846:Bone Development / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002352:Carrier Proteins / Q000494:pharmacology; D002454:Cell Differentiation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D002478:Cells, Cultured; D004396:Coloring Agents; D017930:Genes, Reporter; D007150:Immunohistochemistry; D051379:Mice; D010006:Osteoblasts / Q000187:drug effects*; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D012886:Skull / Q000166:cytology / Q000187:drug effects; D014315:Triterpenes / Q000494:pharmacology*; D000097245:Ursolic Acid; D000099176:Noggin Protein
D000469:Alkaline Phosphatase; D045930:Anabolic Agents; D000880:Anthraquinones; D002118:Calcium; D002352:Carrier Proteins; D004396:Coloring Agents; D012333:RNA, Messenger; D014315:Triterpenes; D000097245:Ursolic Acid; D000099176:Noggin Protein; C004468:Alizarin Red S