title: Core level regulatory network of osteoblast as molecular mechanism for osteoporosis and treatment.
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 state.
authors.affiliation: Key Laboratory of Systems Biomedicine, Ministry of Education, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.|School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Ruoshi
authors.initials: R
authors.lastname: Yuan
authors.affiliation: Department of Physics, East China Normal University, Shanghai, China.
authors.forename: Shengfei
authors.initials: S
authors.lastname: Ma
authors.affiliation: GeneMath, N.E., Seattle, WA, USA.
authors.forename: Xiaomei
authors.initials: X
authors.lastname: Zhu
authors.affiliation: The Center for Anti-Ageing and Regenerative Medicine, Shenzhen University, Shenzhen, China.
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.affiliation: The Center for Anti-Ageing and Regenerative Medicine, Shenzhen University, Shenzhen, China.
authors.forename: Yuhong
authors.initials: Y
authors.lastname: Liang
authors.affiliation: The Center for Anti-Ageing and Regenerative Medicine, Shenzhen University, Shenzhen, China.
authors.forename: Tao
authors.initials: T
authors.lastname: Liu
authors.affiliation: The Center for Anti-Ageing and Regenerative Medicine, Shenzhen University, Shenzhen, China.
authors.forename: Yanxia
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: The Center for Anti-Ageing and Regenerative Medicine, Shenzhen University, Shenzhen, China.
authors.forename: Bingbing
authors.initials: B
authors.lastname: Zhang
authors.affiliation: The Center for Anti-Ageing and Regenerative Medicine, Shenzhen University, Shenzhen, China.
authors.forename: Shuang
authors.initials: S
authors.lastname: Tan
authors.affiliation: The Center for Anti-Ageing and Regenerative Medicine, Shenzhen University, Shenzhen, China.
authors.forename: Huajie
authors.initials: H
authors.lastname: Guo
authors.affiliation: Department of Physics, East China Normal University, Shanghai, China.
authors.forename: Shuguang
authors.initials: S
authors.lastname: Guan
authors.affiliation: Key Laboratory of Systems Biomedicine, Ministry of Education, Shanghai Center for Systems Biomedicine, Shanghai Jiao Tong University, Shanghai, China.|School of Biomedical Engineering, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Ping
authors.initials: P
authors.lastname: Ao
authors.affiliation: The Center for Anti-Ageing and Regenerative Medicine, Shenzhen University, Shenzhen, China.
authors.forename: Guangqian
authors.initials: G
authors.lastname: Zhou
mesh_terms: D000818:Animals; D002478:Cells, Cultured; D005260:Female; D020869:Gene Expression Profiling; D053263:Gene Regulatory Networks / Q000187:drug effects*; D008958:Models, Molecular; D010006:Osteoblasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D010024:Osteoporosis / Q000188:drug therapy* / Q000235:genetics*; D010052:Ovariectomy; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects*; D013324:Strontium / Q000494:pharmacology*
chemical_list: D013324:Strontium
keywords: Gerotarget; hormone; osteoporosis; regulatory network; strontium treatment; systems biology