| RRC ID |
18211
|
| 著者 |
Yonezawa T, Lee JW, Hibino A, Asai M, Hojo H, Cha BY, Teruya T, Nagai K, Chung UI, Yagasaki K, Woo JT.
|
| タイトル |
Harmine promotes osteoblast differentiation through bone morphogenetic protein signaling.
|
| ジャーナル |
Biochem Biophys Res Commun
|
| Abstract |
Bone mass is regulated by osteoblast-mediated bone formation and osteoclast-mediated bone resorption. We previously reported that harmine, a β-carboline alkaloid, inhibits osteoclast differentiation and bone resorption in vitro and in vivo. In this study, we investigated the effects of harmine on osteoblast proliferation, differentiation and mineralization. Harmine promoted alkaline phosphatase (ALP) activity in MC3T3-E1 cells without affecting their proliferation. Harmine also increased the mRNA expressions of the osteoblast marker genes ALP and Osteocalcin. Furthermore, the mineralization of MC3T3-E1 cells was enhanced by treatment with harmine. Harmine also induced osteoblast differentiation in primary calvarial osteoblasts and mesenchymal stem cell line C3H10T1/2 cells. Structure-activity relationship studies using harmine-related β-carboline alkaloids revealed that the C3-C4 double bond and 7-hydroxy or 7-methoxy group of harmine were important for its osteogenic activity. The bone morphogenetic protein (BMP) antagonist noggin and its receptor kinase inhibitors dorsomorphin and LDN-193189 attenuated harmine-promoted ALP activity. In addition, harmine increased the mRNA expressions of Bmp-2, Bmp-4, Bmp-6, Bmp-7 and its target gene Id1. Harmine also enhanced the mRNA expressions of Runx2 and Osterix, which are key transcription factors in osteoblast differentiation. Furthermore, BMP-responsive and Runx2-responsive reporters were activated by harmine treatment. Taken together, these results indicate that harmine enhances osteoblast differentiation probably by inducing the expressions of BMPs and activating BMP and Runx2 pathways. Our findings suggest that harmine has bone anabolic effects and may be useful for the treatment of bone-decreasing diseases and bone regeneration as a lead compound.
|
| 巻・号 |
409(2)
|
| ページ |
260-5
|
| 公開日 |
2011-6-3
|
| DOI |
10.1016/j.bbrc.2011.05.001
|
| PII |
S0006-291X(11)00747-9
|
| PMID |
21570953
|
| MeSH |
Animals
Bone Morphogenetic Proteins / metabolism*
Bone Morphogenetic Proteins / pharmacology
Carbolines / chemistry
Carbolines / pharmacology
Cell Differentiation / drug effects*
Cell Differentiation / genetics
Cell Line
Core Binding Factor Alpha 1 Subunit / genetics
Gene Expression / drug effects
Harmine / chemistry
Harmine / pharmacology*
Humans
Inhibitor of Differentiation Protein 1 / genetics
Mice
Mice, Inbred Strains
Osteoblasts / cytology
Osteoblasts / drug effects*
Osteoblasts / metabolism
Osteogenesis / drug effects*
Osteogenesis / genetics
Signal Transduction
Skull / cytology
Sp7 Transcription Factor
Structure-Activity Relationship
Transcription Factors / genetics
|
| IF |
2.985
|
| 引用数 |
43
|
|
WOS 分野
|
BIOPHYSICS
BIOCHEMISTRY & MOLECULAR BIOLOGY
|
| リソース情報 |
| ヒト・動物細胞 |
MC3T3-E1(RCB1126) |
