Higenamine promotes osteogenesis via IQGAP1/SMAD4 signaling pathway and prevents age-and estrogen-dependent bone loss in mice
Dong, Hui Liu, Ronghan Zou, Ke Jin, Zhengxin Kang, Jianning Zhang, Ying Zhang, Xiaodi Sun, Zhengfang Yu, Guilian Huang, Nana
Dong, Hui
Liu, Ronghan
Zou, Ke
Jin, Zhengxin
Kang, Jianning
Zhang, Ying
Zhang, Xiaodi
Sun, Zhengfang
Yu, Guilian
Huang, Nana
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2023-03-12
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Article
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Keywords
Osteoporosis,Osteoblast,Higenamine,SMAD family,IQGAP1
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Citation
Dong, H., Liu, R., Zou, K., Jin, Z., Kang, J., Zhang, Y., Zhang, X., Sun, Z., Yu, G., Huang, N., Bretches, M., Yang, S.-Y. and Ning, B. (2023), Higenamine Promotes Osteogenesis Via IQGAP1/SMAD4 Signaling Pathway and Prevents Age- and Estrogen-Dependent Bone Loss in Mice. J Bone Miner Res. https://doi.org/10.1002/jbmr.4800
Abstract
Osteoporosis is a common bone disease caused by an imbalance of bone resorption and formation that results in a loss of total bone density. SMAD2/3 signal transduction is known to play a crucial role in osteogenic differentiation through transforming growth factor-beta (TGF-?). By screening a library of small-molecule compounds, the current study identifies higenamine (HG) as an active osteogenic agent that could be a therapeutic candidate for osteoporosis. In vitro data demonstrated that HG effectively induced expressions of osteogenic markers in mouse bone marrow stromal cell (BMSCs) and preosteoblastic cell cultures. Further, HG treatment resulted in enhanced bone formation and prevented accelerated bone loss on two animal models that mimic spontaneous senile osteoporosis and postmenopausal osteoporosis. IQ motif-containing GTPase-activating protein 1 (IQGAP1) was confirmed as a novel target of HG, where HG appears to bind to the Glu-1019 site of IQGAP1 to exert its osteogenic effects. Data subsequently suggested that HG promoted phosphorylation of SMAD2/3 and regulated the SMAD2/3 pathway by inhibiting SMAD4 ubiquitination. Overall, the findings highlight HG as a new small-molecule drug to promote bone formation through SMAD2/3 pathway in osteoporosis.
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Publisher
John Wiley and Sons Inc
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Journal of Bone and Mineral Research
2023
2023
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0884-0431