title: Osteoinductive small molecules: growth factor alternatives for bone tissue engineering.
abstract: Tissue engineering aims to repair, restore, and regenerate lost or damaged tissues by using biomaterials, cells, mechanical forces and factors (chemical and biological) alone or in combination. Growth factors are routinely used in the tissue engineering approach to expedite the process of regeneration. The growth factor approach has been hampered by several complications including high dose requirements, lower half-life, protein instability, higher costs and undesired side effects. Recently a variety of alternative small molecules of both natural and synthetic origin have been explored as alternatives to growth factors for tissue regeneration applications. Small molecules are simple biochemical components that elicit certain cellular responses through signaling cascades. Small molecules present a viable alternative to biological factors. Small molecule strategies can reduce various side effects, maintain bioactivity in a biological environment and minimize cost issues associated with complex biological growth factors. This manuscript focuses on three-osteoinductive small molecules, namely melatonin, resveratrol (from natural sources) and purmorphamine (synthetically designed) as inducers of bone formation and osteogenic differentiation of stem cells. Efforts have been made to summarize possible biological pathways involved in the action of each of these drugs. Melatonin is known to affect Mitogen Activated Protein (MAP) kinase, Bone morphogenic protein (BMP) and canonical wnt signaling. Resveratrol is known to activate cascades involving Wnt and NAD-dependent deacetylase sirtuin-1 (Sirt1). Purmorphamine is a Hedgehog (Hh) pathway agonist as it acts on Smoothened (Smo) receptors. These mechanisms and the way they are affected by the respective small molecules will also be discussed in the manuscript.
authors: Institute for Regenerative Engineering, and Raymond and Beverly Sackler Center for Biological, Physical and Engineering Sciences, The University of Connecticut, Farmington, CT 06030-3711, USA.
authors: Aja
authors: A
authors: Aravamudhan
authors: Daisy M
authors: DM
authors: Ramos
authors: Jonathan
authors: J
authors: Nip
authors: Aditi
authors: A
authors: Subramanian
authors: Roshan
authors: R
authors: James
authors: Matthew D
authors: MD
authors: Harmon
authors: Xiaojun
authors: X
authors: Yu
authors: Sangamesh G
authors: SG
authors: Kumbar
mesh_terms: D000818:Animals; D001861:Bone Regeneration / Q000187:drug effects*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D015394:Molecular Structure; D010012:Osteogenesis / Q000187:drug effects*; D015398:Signal Transduction; D054852:Small Molecule Libraries / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D023822:Tissue Engineering / Q000379:methods*
chemical_list: D036341:Intercellular Signaling Peptides and Proteins; D054852:Small Molecule Libraries