2, 6, 9-Trisubstituted purine derivatives regulating osteogenic differentiation of C2C12 cells and MC3T3 cells Rakhi Bormon 1 , Ekta Srivastava 2 , Ashok Kumar* 2346 , Sandeep Verma* 13456 1 Department of Chemistry, Indian Institute of Technology Kanpur, India, 2 Department of Biological Sciences & Bioengineering, Indian Institute of Technology Kanpur, India, 3 Centre for Environmental Science and Engineering, Indian Institute of Technology Kanpur, India, 4 Centre for Nanosciences, Indian Institute of Technology Kanpur, India, 5 Gangwal School of Medical Sciences and Technology, Indian Institute of Technology Kanpur, India, 6 The Mehta family centre for engineering in Medicine, Indian Institute of Technology Kanpur, India Osteoporosis is a common age-related skeletal disease affecting over 200 million people worldwide. 1 It is also considered a silent disease because of its asymptomatic behavior until a fracture happens. The reported therapeutic drugs so far are mainly antiresorptive drugs having many side effects. 2 Therefore cell-based therapy is considered one of the prominent methods for the treatment of bone-related diseases. Cells having the potential of differentiating or dedifferentiating into bone-forming cells (osteoblasts) can be used for this purpose. 3 Purines and their analogs have the potential for inducing osteogenic differentiation of different cell lineages. 4,5 These kinds of molecules are found to enhance the expression of different osteogenic markers such as alkaline phosphatase (ALP), Runx3, bone morphogenetic proteins (BMPs), etc., and decide the cellular fate. Here, we designed and synthesized two 2, 6, 9-trisubstituted purine derivatives that induce osteogenic differentiation of two different cell lines such as C2C12 cell line (myoblasts cell line) and MC3T3 cell line (osteoblast precursor cell line). The derivatives induce the expression of early osteogenic marker alkaline phosphatase (ALP) and calcium deposition indicating the formation of new bone cells. Such substituted purine derivatives can serve as potential therapeutic for bone fractures through cell-based therapy. This kind of drug-incorporated cell-based therapy has a high potential for bone tissue engineering.
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