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Effect of Small Chemicals like N‐Methyl Pyrrolidone (NMP) on the Orchestration of Bone Remodeling by Osteocytes
Author(s) -
Siegenthaler Barbara,
Ghayor Chafik,
Weber Franz
Publication year - 2015
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.29.1_supplement.1027.4
Subject(s) - sclerostin , chemistry , osteocyte , osteoblast , wnt signaling pathway , microbiology and biotechnology , rankl , bone cell , alkaline phosphatase , osteoporosis , bone remodeling , medicine , receptor , endocrinology , signal transduction , biochemistry , biology , in vitro , activator (genetics) , enzyme
Osteoporosis is a bone disease that is characterized by gradually decreasing bone mass and hence increasing fracture risk with age. This bone mass is regulated by a tightly controlled balance between osteoblasts and osteoclasts orchestrated by osteocytes. Mediators of this orchestration are nitric oxide, RANKL, prostaglandin, and Sclerostin. The latter is expressed by mature osteocytes and has been shown to compete with Wnt signaling, thereby negatively regulating bone formation. Recently our lab identified N‐Methyl Pyrrolidone (NMP) as a potent agent for bone regeneration on the level of osteoblasts and osteoclasts. The aim of this study was to characterize the effect of NMP and NMP‐like small molecules on osteocytes. We used the mouse osteocytic cell line IDG‐SW3 and the rat mature osteoblast cell line UMR‐106 to investigate the effect of small the chemicals on the expression levels of Sclerostin. Chemical treatment was performed in different concentrations over multiple weeks. Cell viability was measured to investigate for toxic chemical concentrations and Alkaline Phosphatase activity assays were performed to check the cellular potential of calcium deposition. Furthermore, total RNA was isolated and real time PCR performed to assess for gene expression alterations with the different treatments. Our preliminary results indicate the NMP and NMLs are capable to reduce sclerostin expression and thereby could possibly diminish the competitive binding to the LRP5/6 receptors and facilitate bone formation. Further experiments are needed to investigate the effect of NMP and NMLs on bone cells to understand the molecular and cellular basis of their possible anti‐osteoporotic potential.