Abstract
Bone remodeling is sustained by the balance between the osteoclast-mediated bone resorption and the osteoblastmediated bone formation. 1 Old bone is resorbed by matured osteoclasts that are derived from hematopoietic stem cells of the monocyte/macrophage lineage by the receptor activator of NF-κB ligand (RANKL) and then the resorbed area is newly filled with new bone matrix that is synthesized by osteoblasts. Osteoblast-mediated bone formation is also the highly regulated and sequential process. Mesenchymal stem cells (MSCs) initially commit to pre-osteoblasts by bone morphogenetic proteins (BMPs) and subsequently those are matured into osteoblasts, the essential for bone mineralization. However, the imbalance in bone remodeling caused by the over-activation of osteoclasts and/or the reduced activity of osteoblasts leads to the loss of bone mass that is a major cause of several bone disorders such as osteoporosis. The loss of bone mass in the elder is not directly mortal, but it can increase the risk of fractures that can threat the quality of life by serious problems such as substantial skeletal deformity, pain, increased mortality, and severe economic burden for the treatment. 2 Therefore, including the combination therapy of anabolic agents with anti-resorptive agent, the development of anti-osteoporotic small molecules with dual mode of action, decreasing bone resorption (anti-resorptive activity) and increasing bone formation (anabolic activity) has become a growing area of interest. 3 Interestingly, in this study, we found that methyl 3-(3,5dimethoxyphenyl)-6-methoxybenzofuran-4-carboxylate (1; Fig. 1) inhibited the RANKL-induced osteoclastogenesis and enhanced the BMP-2-induced osteoblastogenesis by using phenotype-based screening assays. Compound 1 was synthesized as one of intermediates for the total synthesis of oligostilbenoid natural products that exhibit a wide variety of pharmacological activities. 4 Murine RAW264.7 macrophage cells used in this study have been shown to retain the ability to differentiate into multinucleated osteoclasts in the presence of RANKL. Additionally, when treated with RANKL, RAW264.7 cells express high levels of osteoclast-associated genes such as
Published Version (
Free)
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 call