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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creator | Ifegwu, Okechukwu Clinton Awale, Guleid Kan, Ho Man Rajpura, Komal O’Neill, Edward Kuo, Chia-Ling Lo, Kevin W.-H. |
description | 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. |
doi_str_mv | 10.1007/s40883-018-0063-1 |
format | Article |
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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.</description><identifier>ISSN: 2364-4133</identifier><identifier>EISSN: 2364-4141</identifier><identifier>DOI: 10.1007/s40883-018-0063-1</identifier><language>eng</language><publisher>Cham: Springer International Publishing</publisher><subject>Biocompatibility ; Biomaterials ; Biomedical Engineering and Bioengineering ; Biomedical materials ; Chemical compounds ; Chemistry and Materials Science ; Cyclic AMP ; Grafting ; Grafts ; Growth factors ; Kinases ; Materials Science ; Organs ; Osteoblasts ; Pharmacology ; Proteins ; Regeneration (physiology) ; Regenerative Medicine/Tissue Engineering ; Side effects ; Substitute bone ; Toxicity</subject><ispartof>Regenerative engineering and translational medicine, 2018-12, Vol.4 (4), p.206-215</ispartof><rights>The Regenerative Engineering Society 2018</rights><rights>Copyright Springer Science & Business Media 2018</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c353t-dca14f9400460550998c1579fe88ee7d544b869226bf09939d1eccc328ae8e633</citedby><cites>FETCH-LOGICAL-c353t-dca14f9400460550998c1579fe88ee7d544b869226bf09939d1eccc328ae8e633</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://link.springer.com/content/pdf/10.1007/s40883-018-0063-1$$EPDF$$P50$$Gspringer$$H</linktopdf><linktohtml>$$Uhttps://link.springer.com/10.1007/s40883-018-0063-1$$EHTML$$P50$$Gspringer$$H</linktohtml><link.rule.ids>314,780,784,27924,27925,41488,42557,51319</link.rule.ids></links><search><creatorcontrib>Ifegwu, Okechukwu Clinton</creatorcontrib><creatorcontrib>Awale, Guleid</creatorcontrib><creatorcontrib>Kan, Ho Man</creatorcontrib><creatorcontrib>Rajpura, Komal</creatorcontrib><creatorcontrib>O’Neill, Edward</creatorcontrib><creatorcontrib>Kuo, Chia-Ling</creatorcontrib><creatorcontrib>Lo, Kevin W.-H.</creatorcontrib><title>Bone Regenerative Engineering Using a Protein Kinase A-Specific Cyclic AMP Analogue Administered for Short Term</title><title>Regenerative engineering and translational medicine</title><addtitle>Regen. Eng. Transl. Med</addtitle><description>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.</description><subject>Biocompatibility</subject><subject>Biomaterials</subject><subject>Biomedical Engineering and Bioengineering</subject><subject>Biomedical materials</subject><subject>Chemical compounds</subject><subject>Chemistry and Materials Science</subject><subject>Cyclic AMP</subject><subject>Grafting</subject><subject>Grafts</subject><subject>Growth factors</subject><subject>Kinases</subject><subject>Materials Science</subject><subject>Organs</subject><subject>Osteoblasts</subject><subject>Pharmacology</subject><subject>Proteins</subject><subject>Regeneration (physiology)</subject><subject>Regenerative Medicine/Tissue Engineering</subject><subject>Side effects</subject><subject>Substitute bone</subject><subject>Toxicity</subject><issn>2364-4133</issn><issn>2364-4141</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2018</creationdate><recordtype>article</recordtype><recordid>eNp1kN1LwzAUxYsoOOb-AN8CPlfz1Sx9rGN-4MThtufQpbc1Y0tq0gn7702p6JMv91w451wuvyS5JviWYDy9CxxLyVJMZIqxYCk5S0aUCZ5ywsn5787YZTIJYYdxTFIhZDZK3L2zgN6hAQu-7MwXoLltjAXwxjZoE_pZoqV3HRiLXowtA6AiXbWgTW00mp30PkrxukSFLfeuOUa7OhhrQgceKlQ7j1YfzndoDf5wlVzU5T7A5EfHyeZhvp49pYu3x-dZsUg1y1iXVrokvM45xlzgLMN5LjXJpnkNUgJMq4zzrRQ5pWJbR5PlFQGtNaOyBAmCsXFyM9xtvfs8QujUzh19fDAoSpjIcioIjykypLR3IXioVevNofQnRbDq0aoBrYrAVI9WkdihQye0PSLwf5f_L30DxFR6iQ</recordid><startdate>20181201</startdate><enddate>20181201</enddate><creator>Ifegwu, Okechukwu Clinton</creator><creator>Awale, Guleid</creator><creator>Kan, Ho Man</creator><creator>Rajpura, Komal</creator><creator>O’Neill, Edward</creator><creator>Kuo, Chia-Ling</creator><creator>Lo, Kevin W.-H.</creator><general>Springer International Publishing</general><general>Springer Nature B.V</general><scope>AAYXX</scope><scope>CITATION</scope></search><sort><creationdate>20181201</creationdate><title>Bone Regenerative Engineering Using a Protein Kinase A-Specific Cyclic AMP Analogue Administered for Short Term</title><author>Ifegwu, Okechukwu Clinton ; Awale, Guleid ; Kan, Ho Man ; Rajpura, Komal ; O’Neill, Edward ; Kuo, Chia-Ling ; Lo, Kevin W.-H.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c353t-dca14f9400460550998c1579fe88ee7d544b869226bf09939d1eccc328ae8e633</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2018</creationdate><topic>Biocompatibility</topic><topic>Biomaterials</topic><topic>Biomedical Engineering and Bioengineering</topic><topic>Biomedical materials</topic><topic>Chemical compounds</topic><topic>Chemistry and Materials Science</topic><topic>Cyclic AMP</topic><topic>Grafting</topic><topic>Grafts</topic><topic>Growth factors</topic><topic>Kinases</topic><topic>Materials Science</topic><topic>Organs</topic><topic>Osteoblasts</topic><topic>Pharmacology</topic><topic>Proteins</topic><topic>Regeneration (physiology)</topic><topic>Regenerative Medicine/Tissue Engineering</topic><topic>Side effects</topic><topic>Substitute bone</topic><topic>Toxicity</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ifegwu, Okechukwu Clinton</creatorcontrib><creatorcontrib>Awale, Guleid</creatorcontrib><creatorcontrib>Kan, Ho Man</creatorcontrib><creatorcontrib>Rajpura, Komal</creatorcontrib><creatorcontrib>O’Neill, Edward</creatorcontrib><creatorcontrib>Kuo, Chia-Ling</creatorcontrib><creatorcontrib>Lo, Kevin W.-H.</creatorcontrib><collection>CrossRef</collection><jtitle>Regenerative engineering and translational medicine</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ifegwu, Okechukwu Clinton</au><au>Awale, Guleid</au><au>Kan, Ho Man</au><au>Rajpura, Komal</au><au>O’Neill, Edward</au><au>Kuo, Chia-Ling</au><au>Lo, Kevin W.-H.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Bone Regenerative Engineering Using a Protein Kinase A-Specific Cyclic AMP Analogue Administered for Short Term</atitle><jtitle>Regenerative engineering and translational medicine</jtitle><stitle>Regen. Eng. Transl. Med</stitle><date>2018-12-01</date><risdate>2018</risdate><volume>4</volume><issue>4</issue><spage>206</spage><epage>215</epage><pages>206-215</pages><issn>2364-4133</issn><eissn>2364-4141</eissn><abstract>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.</abstract><cop>Cham</cop><pub>Springer International Publishing</pub><doi>10.1007/s40883-018-0063-1</doi><tpages>10</tpages></addata></record> |
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subjects | Biocompatibility Biomaterials Biomedical Engineering and Bioengineering Biomedical materials Chemical compounds Chemistry and Materials Science Cyclic AMP Grafting Grafts Growth factors Kinases Materials Science Organs Osteoblasts Pharmacology Proteins Regeneration (physiology) Regenerative Medicine/Tissue Engineering Side effects Substitute bone Toxicity |
title | Bone Regenerative Engineering Using a Protein Kinase A-Specific Cyclic AMP Analogue Administered for Short Term |
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