Betulin Suppresses Osteoclast Formation via Down-Regulating NFATc1

• Main Authors: Kwang-Jin Kim, Yongjin Lee, Hae-Gwang Hwang, Sang Hyun Sung, Mina Lee, Young-Jin Son
• Format: Article
• Language: English
• Published: MDPI AG 2018-06-01
• Series: Journal of Clinical Medicine
• Subjects: bone; osteoporosis; osteoclast; RANKL; NFATc1; betulin; natural product; Betula platyphylla
• Online Access: http://www.mdpi.com/2077-0383/7/6/154

Osteoporosis is a disease characterized by osteoclast-mediated low bone mass. The modulation of osteoclasts is important for the prevention or therapeutic treatment of loss of bone mass. Osteoclasts, which are bone-resorbing multinucleated cells, are differentiated from the hematopoietic stem cell monocyte/macrophage lineage by Receptor activator of nuclear factor kappa-B ligand (RANKL) expressed from osteoblasts and stromal cells. RANKL signaling ultimately activates nuclear factor of activated T Cells 1 (NFATc1), which is a master transcription factor in osteoclastogenesis. Betulin, a lupine type pentacyclic triterpenoid, was isolated from the bark of Betula platyphylla. Betulin inhibited RANKL-mediated osteoclast differentiation by downregulating NFATc1. Betulin may serve as a useful structural scaffold in the therapeutic agent development to prevention/treatment the osteoclast-mediated bone disorder.