Asperpyrone A attenuates RANKL‐induced osteoclast formation through inhibiting NFATc1, Ca²⁺ signalling and oxidative stress

Abstract

Imbalance of osteoblast and osteoclast in adult leads to a variety of bone‐related diseases, including osteoporosis. Thus, suppressing the activity of osteoclastic bone resorption becomes the main therapeutic strategy for osteoporosis. Asperpyrone A is a natural compound isolated from Aspergillus niger with various biological activities of antitumour, antimicrobial and antioxidant. The present study was designed to investigate the effects of Asperpyrone A on osteoclastogenesis and to explore its underlining mechanism. We found that Asperpyrone A inhibited RANKL‐induced osteoclastogenesis in a dose‐dependent manner when the concentration reached 1 µm, and with no cytotoxicity until the concentration reached to 10 µm. In addition, Asperpyrone A down‐regulated the mRNA and protein expression of NFATc1, c‐fos and V‐ATPase‐d2, as well as the mRNA expression of TRAcP and Ctsk. Furthermore, Asperpyrone A strongly attenuated the RNAKL‐induced intracellular Ca2+ oscillations and ROS (reactive oxygen species) production in the process of osteoclastogenesis and suppressed the activation of MAPK and NF‐κB signalling pathways. Collectively, Asperpyrone A attenuates RANKL‐induced osteoclast formation via suppressing NFATc1, Ca2+ signalling and oxidative stress, as well as MAPK and NF‐κB signalling pathways, indicating that this compound may become a potential candidate drug for the prevention or treatment of osteoporosis.

Peiminine Suppresses RANKL-Induced Osteoclastogenesis by Inhibiting the NFATc1, ERK, and NF-κB Signaling Pathways

“…BMMs were seeded in plates (96-well plate) at a concentration of 8×10 3 cells per well and cultured in a-MEM (Thermo Fisher Scientific, CA, USA) supplemented with 50 ng/ml M-CSF (R&D Systems, MN, USA) overnight according to the method published by Jin and Chen in 2019 (7,26). After adherence, the BMMs were stimulated with GST-rRANKL (50 ng/ml) (R&D Systems, MN, USA), and peiminine (Feiyubio, Jiangsu, China, CAS no.…”

Imperatorin promotes osteogenesis and suppresses osteoclast by activating AKT/GSK3 β/β‐catenin pathways

“…Although these drugs showed inhibitory effect on osteoclast activity, they had no effect on osteogenic activity. [14][15][16] Simply reducing osteoclast activity may interfere with bone formation, reduce bone transformation and bring side effects such as mandibular osteonecrosis. Studies have shown that the proliferation of early osteoclasts requires the activation of β-catenin; however, the activated β-catenin inhibits the differentiation of osteoclasts.…”

Inhibitory Effects of Rhaponticin on Osteoclast Formation and Resorption by Targeting RANKL-Induced NFATc1 and ROS Activity

“…Therefore, alternative therapeutic agents to prevent osteolytic diseases are urgent to be exploited. Many herbs have been proved possessing the effects to treat osteoporosis ( Chen et al, 2019 ; Jin et al, 2019 ). RH, an important stilbene-type component extracted from the root of Rheum undulatum L. , possesses various biological activities, such as anti-allergic, anti-cancer, anti-diabetic and anti-inflammatory activities in the previous reports (A.…”