Abstract
Osteoporosis is a chronic disease that has become a serious public health problem due to the associated reduction in quality of life and its increasing financial burden. It is known that inhibiting osteoclast differentiation and promoting osteoblast formation prevents osteoporosis. As there is no drug with this dual activity without clinical side effects, new alternatives are needed. Here, we demonstrate that austalide K, isolated from the marine fungus Penicillium rudallenes, has dual activities in bone remodeling. Austalide K inhibits the receptor activator of nuclear factor-κB ligand (RANKL)-induced osteoclast differentiation and improves bone morphogenetic protein (BMP)-2-mediated osteoblast differentiation in vitro without cytotoxicity. The nuclear factor of activated T cells c1 (NFATc1), tartrate-resistant acid phosphatase (TRAP), dendritic cell-specific transmembrane protein (DC-STAMP), and cathepsin K (CTSK) osteoclast-formation-related genes were reduced and alkaline phosphatase (ALP), runt-related transcription factor 2 (Runx2), osteocalcin (OCN), and osteopontin (OPN) (osteoblast activation-related genes) were simultaneously upregulated by treatment with austalide K. Furthermore, austalide K showed good efficacy in an LPS-induced bone loss in vivo model. Bone volume, trabecular separation, trabecular thickness, and bone mineral density were recovered by austalide K. On the basis of these results, austalide K may lead to new drug treatments for bone diseases such as osteoporosis.
Highlights
Osteoporosis is an age- and sex-related disease for which postmenopausal women are at the greatest risk [1]
Osteoclasts derived from hematopoietic stem cells are activated for resorption from dormant bones covered with inactive osteoblasts by cytokines such as RANKL and macrophage colony-stimulating factor (M-CSF)
Using bioactivity-guided fractionation, we discovered a dual-functional natural product that can be isolated from the marine fungus Penicillium rudallense
Summary
Osteoporosis is an age- and sex-related disease for which postmenopausal women are at the greatest risk [1]. In addition to postmenopausal osteoporosis, bone remodeling plays an important role in rheumatoid arthritis, periodontitis, and Paget’s disease. The multinucleated osteoclasts attach to the bone surface via the avb integrin receptor and produce protons with the help of carbonic anhydrase II (CA II) and vacuolar H+ -ATPase. This resorption process lasts about 3 weeks, using the chloride channel-7 (CLC7), protease CTSK enzyme, and acid. IGF signaling, which controls the differentiation of parathyroid hormone, growth hormone, and osteoblasts, plays an important role, resulting in osteoblasts forming a collagenous bone matrix and subsequently in mineralization. If the balance between osteoclast and osteoblast activity is disrupted, it leads to an increased possibility of bone fractures [4,5,6,7]
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.
