The cyclic AMP signaling pathway: Exploring targets for successful drug discovery (Review). Yan K, Gao L-N, Cui Y-L, Zhang Y, Zhou X. Subcellular Organization of the cAMP Signaling Pathway. Phenotypic screens as a renewed approach for drug discovery. The Power of Sophisticated Phenotypic Screening and Modern Mechanism-of-Action Methods. Mesenchymal Stem Cells Current Clinical Applications: A Systematic Review. Rodríguez-Fuentes DE, Fernández-Garza LE, Samia-Meza JA, Barrera-Barrera SA, Caplan AI, Barrera-Saldaña HA. Mesenchymal stem cells: amazing remedies for bone and cartilage defects. Kangari P, Talaei-Khozani T, Razeghian-Jahromi I, Razmkhah M. Mesenchymal Stem Cells in Bone Regeneration. Drug repurposing: progress, challenges and recommendations. Delivery of small molecules for bone regenerative engineering: preclinical studies and potential clinical applications. Laurencin CT, Ashe KM, Henry N, Kan HM, Lo KW-H. Engineered Bone Tissue with Naturally-Derived Small Molecules. Osteoinductive Small Molecules: Growth Factor Alternatives for Bone Tissue Engineering. Studies of bone morphogenetic protein-based surgical repair. Lo KW-H, Ulery BD, Ashe KM, Laurencin CT. This study describes the evaluation of cAMP analogues and activating small molecules that can be used as alternative treatment options to rhBMPs in bone repair. Therefore, efforts have been made to discover and repurpose small molecule therapeutics to promote bone regeneration. However, significant limitations such as instability, low solubility, immunogenicity, high production cost, and the potential risk of disease transmission of these therapies remain. Recombinant human bone morphogenetic proteins (rhBMPs) are therapeutic agents that have been widely used by orthopaedic surgeons to stimulate bone tissue formation when paired with biomaterials. Lay Summaryīone grafting procedures have become increasingly common in the United States, with approximately 500,000 cases occurring each year at a societal cost exceeding $2.5 billion. Overall, by inducing the osteogenic differentiation of mesenchymal stem cells with a single-dose of forskolin and without requiring repeated forskolin administration shows great potential for bone regenerative engineering applications. In addition, we compared the effects of single-dose and repeat-dose forskolin treatment towards inducing osteogenic differentiation of rBMSCs. Our results demonstrated that the treatment of the small molecule forskolin (100 µM) for 24 h significantly increased the osteogenic differentiation and mineralization of rabbit adipose-derived stem cells (rADSCs) and rabbit bone marrow-derived stem cells (rBMSCs). In this study, we performed a phenotypic mini-screen of several cAMP analogues and activating small molecules to compare their osteoinductive effects on rabbit mesenchymal stem cells (MSCs). However, the capability of these cAMP small molecules to induce osteogenesis in primary cells such as mesenchymal stem cells using the shorter-term or single-dose treatment approach has yet to be fully evaluated. A promising strategy to mitigate the side-effect risk of small molecule treatments is to reduce their frequency of administration. Previously, we have investigated the capability of various cyclic adenosine monophosphate (cAMP) analogues to induce osteogenic differentiation in vitro using osteoprogenitor MC3T3-E1 cells. However, off-target effects of small molecules due to their short half-life and non-specificity hinder their wide-spread usage. This explains why we can get energy from the starch in potatoes and other plants but not from cellulose, even though both starch and cellulose are polysaccharides composed of glucose molecules linked together.Small molecule-based bone regenerative engineering has been proposed as a promising approach in repairing bone tissue and circumventing the issues associated with protein-based growth factor treatment. The difference between the α and the β forms of sugars may seem trivial, but such structural differences are often crucial in biochemical reactions. Any group written to the right in a Fischer projection appears below the plane of the ring in a Haworth projection, and any group written to the left in a Fischer projection appears above the plane in a Haworth projection. The structure is simplified to show only the functional groups attached to the carbon atoms. The molecules are drawn as planar hexagons with a darkened edge representing the side facing toward the viewer. \)) the cyclic forms of sugars are depicted using a convention first suggested by Walter N.
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