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Applications
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LDN-193189 inhibited both BMP induced Smad1/5/8 phosphorylation and BMP-mediated induction of the p38 MAPK, Erk1/2 and Akt pathway in C2C12 cells. LDN-193189 dose-dependently inhibited the activation of Smad1/5/8, p38 and Akt. LDN-193189 induced a strong increase in phosphorylated p38 MAPK levels and a slight increase in p-Akt in C2C12 cells. LDN (10 μM, 60 min) induced p38 and Akt phosphorylation. LDN (0.5 μM, 30 min) inhibited BMP-mediated Smad1/5/8, p38, ATF2 and CREB phosphorylation.
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Application
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In Ad.Cre-injected, caALK2-expressing mice, treatment with LDN-193189 prevented radiographic lesions at P15. LDN-193189–treated mice appeared to preserve knee and ankle joints at P30 and P60. LDN-193189-treated mice showed no ectopic bone at P15 but did show enhanced cartilage formation in surrounding soft tissues. LDN-193189–treated mice showed mildly impaired range of motion even in the absence of radiographically visible disease at P30.
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References:
[1]. Yu PB, Deng DY, Lai CS, Hong CC, Cuny GD, Bouxsein ML, Hong DW, McManus PM, Katagiri T, Sachidanandan C, Kamiya N, Fukuda T, Mishina Y, Peterson RT, Bloch KD. BMP type I receptor inhibition reduces heterotopic [corrected] ossification. Nat Med. 2008 Dec;14(12):1363-9.
[2]. Yu PB, Deng DY, Lai CS, Hong CC, Cuny GD, Bouxsein ML, Hong DW, McManus PM, Katagiri T, Sachidanandan C, Kamiya N, Fukuda T, Mishina Y, Peterson RT, Bloch KD. BMP type I receptor inhibition reduces heterotopic [corrected] ossification. Nat Med. 2008 Dec;14(12):1363-9.
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