Austalide K from the Fungus Penicillium rudallense Prevents LPS-Induced Bone Loss in Mice by Inhibiting Osteoclast Differentiation and Promoting Osteoblast Differentiation.
Kwang-Jin KimJusung LeeWeihong WangYongjin LeeEunseok OhKyu-Hyung ParkChanyoon ParkGee-Eun WooYoung-Jin SonHeonjoong KangPublished in: International journal of molecular sciences (2021)
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.
Keyphrases
- bone loss
- bone mineral density
- nuclear factor
- lps induced
- postmenopausal women
- toll like receptor
- inflammatory response
- transcription factor
- body composition
- public health
- dendritic cells
- bone regeneration
- mesenchymal stem cells
- signaling pathway
- drug induced
- healthcare
- emergency department
- mass spectrometry
- mouse model
- type diabetes
- skeletal muscle
- stress induced
- wild type
- insulin resistance