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Activation of cyclic amp/protein kinase: A signaling pathway enhances osteoblast cell adhesion on biomaterials for regenerative engineering

Osteoblast cell adhesion on biomaterials is an important goal for implants to be useful in bone regeneration technologies. The adhesion of osteoblastic cells to biomaterials has been investigated in the field of bone regenerative engineering. Previous work from our group demonstrated that osteoblastic cells adhering to biodegradable biomaterials require the expression of integrins on the cell surface. However, the underlying molecular signaling mechanism is still not fully clear. We report here that cyclic adenosine monophosphate (cAMP), a small signaling molecule, regulates osteoblast cell adhesion to biomaterial surfaces. We used an in vitro cell adhesion assay to demonstrate that at 0.1 mM, 8‐Br‐cAMP, a cell‐permeable cAMP analog, significantly enhances osteoblast‐like cells' (MC3T3‐E1) adherence to biomaterials. Moreover, we demonstrate that a commonly used cAMP‐elevating agent, forskolin, promotes cell adhesion similar to that of the cell permeable cAMP analog. By using different target‐specific cAMP analogs: 8‐CPT‐2Me‐cAMP which specifically activates exchange protein activated by cAMP (Epac), and 6‐Bnz‐cAMP which specifically activates protein kinase A (PKA), we observed that the PKA signaling pathway plays a dominant role in this process. Thus, this report suggests a new method to enhance osteoblast cell adhesion on biodegradable biomaterials for bone regenerative engineering applications. © 2010 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res 29:602–608, 2011