Abstract
Receptor activator of nuclear factor-κB ligand (RANKL) is a cytokine responsible for bone resorption. It binds its receptor RANK, which activates osteoporosis. High levels of osteoprotegerin (OPG) competitively binding RANKL limit formation of ligand-receptor complexes and enable bone mass maintenance. The new approach to prevent osteoporosis is searching for therapeutics that can bind RANKL and support OPG function. The aim of the study was to verify the hypothesis that isoflavones can form complexes with RANKL limiting binding of the cytokine to its receptor. Interactions of five isoflavones with RANKL were investigated by isothermal titration calorimetry (ITC), by in silico docking simulation and on Saos-2 cells. Daidzein and biochanin A showed the highest affinity for RANKL. Among studied isoflavones coumestrol, formononetin and biochanin A showed the highest potential for Saos-2 mineralization and were able to regulate the expression of RANKL and OPG at the mRNA levels, as well as osteogenic differentiation markers: alkaline phosphatase (ALP), collagen type 1, and Runt-related transcription factor 2 (Runx2). Comparison of the osteogenic activities of isoflavones showed that the use of physicochemical techniques such as ITC or in silico docking are good tools for the initial selection of substances showing a specific bioactivity.
Highlights
Bone components are completely replaced within 3–10 years, taking place as a result of bone remodeling through cyclical bone formation and resorption processes
Formononetin, and biochanin A showed the highest potential for Saos-2 mineralization and were able to regulate the expression of RANKL and OPG at the mRNA levels, as well as osteogenic differentiation markers: alkaline phosphatase, collagen type 1, and Runt-related transcription factor 2 (Runx2)
Considering the activity of isoflavones as nutraceuticals complexing RANKL helpful in the prevention of osteoporosis, it should be taken into account whether they are administered as isolated individual substances or as a mixture in functional foods
Summary
Bone components are completely replaced within 3–10 years, taking place as a result of bone remodeling through cyclical bone formation and resorption processes. This determines the regenerative capacity of bones, such as healing injuries, wounds, and fractures. Osteoblasts are bone-forming cells, while osteoclasts that are activated by osteoblasts are responsible for their destruction. The signaling pathway through which osteoblasts regulate the level of activated osteoclasts involves a system of three factors: receptor activator of nuclear factor-κB ligand (RANKL)/osteoprotegerin (OPG)/receptor activator of nuclear factor-κB (RANK). RANKL occurs on the surface of osteoblasts and binds RANK found on the membrane of osteoclasts. Osteoclasts differentiate into multinucleated mature forms and transform into activated cells.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
