Identification of osteogenic purmorphamine derivatives.
During embryonic and cancer development, the Hedgehog family of proteins, including Sonic Hedgehog, play an important role by relieving the inhibition of Smo by Ptc, thus activating the Smo signaling cascade. Recently, a purine compound, purmorphamine, has been reported to target the Hedgehog signaling pathway by interacting with Smo. Interestingly, both Sonic Hedgehog and purmorphamine were found to promote the osteogenic differentiation of mouse chondroprogenitor cells. However, there is insufficient information as to how the activation of this seemingly unrelated signaling pathway, either by Sonic Hedgehog or purmorphamine, contributes to osteogenesis. Using alkaline phosphatase assays, we screened 125 purmorphamine derivatives from the Korea Chemical Bank for effects on the differentiation of preosteoblast C2C12 cells. Here, we report that two purine derivatives modulate ALP activity as well as the expression of genes whose expression is known or suggested to be involved in osteogenesis.
Lee
Sung-Jin
SJ
Department of Animal Life Resource Science, Kangwon National University, Chuncheon, Korea.
Lee
Hak-Kyo
HK
Cho
Sung Yun
SY
Choi
Joong-Kwon
JK
Shin
Hea Kyeong
HK
Kwak
Eun-Jung
EJ
Cho
Mi-Ran
MR
Kim
Hye-Ryun
HR
Kim
Seung-Ryol
SR
Kim
Yong-Min
YM
Park
Kyoung-Jin
KJ
Choi
Joong-Kook
JK
D000818:Animals; D016923:Cell Death / Q000187:drug effects; D002454:Cell Differentiation / Q000187:drug effects; D002460:Cell Line; D005786:Gene Expression Regulation / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D051379:Mice; D009025:Morpholines / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology; D020411:Oligonucleotide Array Sequence Analysis; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects; D010012:Osteogenesis / Q000187:drug effects; D011687:Purines / Q000032:analysis* / Q000737:chemistry / Q000494:pharmacology; D020133:Reverse Transcriptase Polymerase Chain Reaction
D009025:Morpholines; D011687:Purines; D007770:L-Lactate Dehydrogenase; C470893:purmorphamine