Corylifol A protects against ovariectomized-induced bone loss and attenuates RANKL-induced osteoclastogenesis via ROS reduction, ERK inhibition, and NFATc1 activation.

Osteoclast differentiation and function are critical targets for anti-osteoporosis treatment. Oxidative stress also plays an important regulatory role in the differentiation of osteoclasts. Corylifol A (CA) is a flavonoid extracted from the Psoralea fruit. It has anti-inflammatory and antioxidant properties despite its unknown effect on osteoporosis. This study found that CA prevented estrogen-deficiency-induced bone loss and suppressed osteoclastogenesis in ovariectomized (OVX) mice by inhibiting intracellular reactive oxygen species (ROS) levels. In vivo, CA effectively prevented trabecular bone loss and reduced osteoclasts' number on the bone surface in OVX mice, as demonstrated in micro-CT, osteometry, and immunohistochemical data. However, CA did not affect cortical bone. In vitro, CA inhibited RANKL-induced podosome belt formation, osteoclastogenesis, and bone resorption functions. CA suppressed RANKL-induced ROS by boosting antioxidant enzymes (Catalase and NQO1) and NFATc1 signaling pathway related protein expression, including integrin αvβ3, NFATc1 and CTSK. Moreover, CA inhibited osteoclast-specific genes, including Ctsk, Acp5, and Mmp9. CA also attenuated the MAPK/ERK pathway, but did not affect the NF-κB signaling pathway. In terms of osteogenesis, CA did not inhibit or promote osteogenic differentiation and mineralization in vitro. These results reveal that CA could be a new replacement therapy for treating estrogen-deficiency osteoporosis via suppressing osteoclastogenesis and intracellular ROS. Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.

Citation

Yinglong Xu, Dezhi Song, Xixi Lin, Hui Peng, Yuangang Su, Jiamin Liang, Na Hai, Jinmin Zhao, Qian Liu. Corylifol A protects against ovariectomized-induced bone loss and attenuates RANKL-induced osteoclastogenesis via ROS reduction, ERK inhibition, and NFATc1 activation. Free radical biology & medicine. 2023 Feb 20;196:121-132

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PMID: 36649902

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