Effects of Growth Factors and Stress Conditioning on the Induction of Heat Shock Proteins and Osteogenesis

Tissue engineering is an emerging field that focuses on development of methods for repairing and regenerating damaged or diseased tissue. Successful development of engineered tissues is often limited by insufficient cellular proliferation and insufficient formation of extracellular matrix. To induce effective bone regeneration, many research groups have investigated the cellular response and capability for tissue regeneration associated with bioreactor conditions and addition of growth factors [1]. Bioreactors in tissue engineering have been developed to expose cells to a similar stress environment as found within the body or induce elevated stress levels for potential induction of specific cellular responses associated with tissue regeneration. Native bone encounters a diverse array of dynamic stresses such as shear, tensile, and compression daily. Stress conditioning protocols in the form of thermal or tensile stress have been shown to induce up-regulation of molecular chaperones called heat shock proteins (HSPs) and bone-related proteins like MMP13 (matrix metallopeptidase 13) [2] and OPG (osteoprotegerin) [3, 4]. HSPs have important roles in enhancing cell proliferation and collagen synthesis. Osteogenic growth factors such as TGF-β1 (transforming growth factor beta 1) and BMP-2 (bone morphogenetic protein 2) are related to bone remodeling and osteogenesis as well as HSP induction [5]. Therefore, identification of effective preconditioning using growth factors and stress protocols that enhance HSP expression could substantially advance development of bone regeneration. The purpose of this research was to identify preconditioning protocols using osteogenic growth factors and tensile stress applied through a bioreactor system to enhance expression of HSPs and bone-related proteins while minimizing cellular injury for ultimate use for bone regeneration.