TY - JOUR
T1 - The l-Ser analog #290 promotes bone recovery in OP and RA mice
AU - Bahtiar, Anton
AU - Nakamura, Takashi
AU - Kishida, Koichi
AU - Katsura, Junpei
AU - Nitta, Mai
AU - Ishida-Kitagawa, Norihiro
AU - Ogawa, Takuya
AU - Takeya, Tatsuo
PY - 2011/9
Y1 - 2011/9
N2 - We previously characterized the l-Ser analog #290, H(tBut)-l-Ser-O- Methyl·HCl, as a novel inhibitor of osteoclastogenesis which functions in both mouse and human cells. Here, we assessed the activity of #290 in animal models of osteoporosis and rheumatoid arthritis. Treatment of animals with #290 both prevented bone loss and led to the recovery of lost bone in osteoporotic mice. When inflammatory arthritis was induced in SKG mice, #290 treatment suppressed arthritis scores and significantly prevented the destruction of calcaneous bones. Additionally, #290 reciprocally modulated the mammalian target of rapamycin (mTOR) pathway in osteoclasts and osteoblasts in vitro, suggesting a dual effect on bone homeostasis. Our results demonstrate that #290 is a potential novel therapeutic tool for the treatment and/or study of diseases associated with bone destruction.
AB - We previously characterized the l-Ser analog #290, H(tBut)-l-Ser-O- Methyl·HCl, as a novel inhibitor of osteoclastogenesis which functions in both mouse and human cells. Here, we assessed the activity of #290 in animal models of osteoporosis and rheumatoid arthritis. Treatment of animals with #290 both prevented bone loss and led to the recovery of lost bone in osteoporotic mice. When inflammatory arthritis was induced in SKG mice, #290 treatment suppressed arthritis scores and significantly prevented the destruction of calcaneous bones. Additionally, #290 reciprocally modulated the mammalian target of rapamycin (mTOR) pathway in osteoclasts and osteoblasts in vitro, suggesting a dual effect on bone homeostasis. Our results demonstrate that #290 is a potential novel therapeutic tool for the treatment and/or study of diseases associated with bone destruction.
KW - Bone loss and recovery
KW - Mouse models
KW - Osteoblastic cells
KW - Osteoclastogenesis inhibitor
KW - l-Ser analog
KW - mTOR
UR - http://www.scopus.com/inward/record.url?scp=79959944605&partnerID=8YFLogxK
U2 - 10.1016/j.phrs.2011.05.004
DO - 10.1016/j.phrs.2011.05.004
M3 - Article
C2 - 21605676
AN - SCOPUS:79959944605
SN - 1043-6618
VL - 64
SP - 203
EP - 209
JO - Pharmacological Research
JF - Pharmacological Research
IS - 3
ER -