Bone Regenerative Engineering Using a Protein Kinase A-Specific Cyclic AMP Analogue Administered for Short Term
Small molecule-mediated bone regeneration is emerging as a promising strategy for replacing or enhancing the therapeutic protein-based growth factors. However, unknown non-specific toxicity of small molecules on non-target cells or organs due to the long-term exposure has been a concern. We previous...
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Veröffentlicht in: | Regenerative engineering and translational medicine 2018-12, Vol.4 (4), p.206-215 |
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Zusammenfassung: | Small molecule-mediated bone regeneration is emerging as a promising strategy for replacing or enhancing the therapeutic protein-based growth factors. However, unknown non-specific toxicity of small molecules on non-target cells or organs due to the long-term exposure has been a concern. We previously demonstrated that the continuous treatment of osteoblast-like MC3T3-E1 cells with small molecule cyclic AMP analogue N
6
-benzoyladenosine-3′,5′-cyclic monophosphate (6-Bnz-cAMP) was capable of inducing in vitro osteogenesis via the protein kinase A (PKA) signaling pathway. In this study, we investigate the effect of short-term 6-Bnz-cAMP treatment, i.e., 1-day treatment, as compared to continuous treatment, on in vitro osteogenesis in osteoprogenitor cells. It is hypothesized that the proposed short-term 6-Bnz-cAMP treatment scheme would result in osteogenesis as in the case of continuous 6-Bnz-cAMP treatment. Our results showed that both short-term and continuous 6-Bnz-cAMP treatments elicited osteoblastic differentiation and mineralization of osteoblast-like MC3T3-E1 cells. Short-term treatment using small molecule 6-Bnz-cAMP can serve as a highly promising strategy for bone regeneration while mitigating potential non-specific side effect risks associated with small molecules.
Lay Summary
The goal of this work is to develop a simple, inexpensive, effective, and safe method to heal bone defect. We would like to treat the bone defects with a small molecule-based therapeutic agent in a short-term treatment so that undesirable side effects from the therapeutics would be significantly minimized. Our work may also result in novel bone graft materials that can potentially become a viable alternative to existing grafts. |
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ISSN: | 2364-4133 2364-4141 |
DOI: | 10.1007/s40883-018-0063-1 |