Core level regulatory network of osteoblast as molecular mechanism for osteoporosis and treatment

Oncotarget
Ruoshi YuanGuangqian Zhou

Abstract

To develop and evaluate the long-term prophylactic treatment for chronic diseases such as osteoporosis requires a clear view of mechanism at the molecular and systems level. While molecular signaling pathway studies for osteoporosis are extensive, a unifying mechanism is missing. In this work, we provide experimental and systems-biology evidences that a tightly connected top-level regulatory network may exist, which governs the normal and osteoporotic phenotypes of osteoblast. Specifically, we constructed a hub-like interaction network from well-documented cross-talks among estrogens, glucocorticoids, retinoic acids, peroxisome proliferator-activated receptor, vitamin D receptor and calcium-signaling pathways. The network was verified with transmission electron microscopy and gene expression profiling for bone tissues of ovariectomized (OVX) rats before and after strontium gluconate (GluSr) treatment. Based on both the network structure and the experimental data, the dynamical modeling predicts calcium and glucocorticoids signaling pathways as targets for GluSr treatment. Modeling results further reveal that in the context of missing estrogen signaling, the GluSr treated state may be an outcome that is closest to the healthy st...Continue Reading

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Citations

Feb 18, 2017·Reports on Progress in Physics·Ruoshi YuanPing Ao
May 9, 2019·International Journal of Molecular Sciences·Li-Ru ChenKuo-Hu Chen
Jun 18, 2020·World Journal of Clinical Cases·Bao-Lin DuanMei-Yi Liu

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Methods Mentioned

BETA
ESR
transmission electron microscopy
electron microscopy
electrophoresis
Feature Extraction

Software Mentioned

Agilent Feature Extraction
GeneSpring GX

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