Isoliensinine Suppresses Osteoclast Formation Through NF-κB Signaling Pathways and Relieves Ovariectomy-Induced Bone Loss

Huijiang Liu; Ronghe Gu; Qian Huang; Yun Liu; Chong Liu; Shijie Liao; Wenyu Feng; Tianyu Xie; Jinmin Zhao; Jiake Xu; Qian Liu; Xinli Zhan

doi:10.3389/fphar.2022.870553

Isoliensinine Suppresses Osteoclast Formation Through NF-κB Signaling Pathways and Relieves Ovariectomy-Induced Bone Loss

Front Pharmacol. 2022 Jul 22:13:870553. doi: 10.3389/fphar.2022.870553. eCollection 2022.

Authors

Huijiang Liu^{1

2

3}, Ronghe Gu^{2

4}, Qian Huang², Yun Liu¹, Chong Liu¹, Shijie Liao¹, Wenyu Feng¹, Tianyu Xie¹, Jinmin Zhao^{1

3}, Jiake Xu⁴, Qian Liu³, Xinli Zhan^{1

3}

Affiliations

¹ Department of Orthopedics, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
² Department of Orthopedics, The First People's Hospital of Nanning, Nanning, China.
³ Guangxi Key Laboratory of Regenerative Medicine, Orthopedic Department, The First Affiliated Hospital of Guangxi Medical University, Nanning, China.
⁴ School of Biomedical Sciences, University of Western Australia, Perth, WA, Australia.

Abstract

Osteoporosis is among the major contributors of pathologic fracture in postmenopausal women, which is caused by the bone metabolic disorder owing to the over-activation of osteoclasts. Inhibition of osteoclast differentiation and maturation has become a mainstream research interest in the prevention of osteoporosis. Isoliensinine (Iso) is a dibenzyl isoquinoline alkaloid with antioxidant, anti-inflammatory, and anti-cancer activities. However, whether it can be used as a potential treatment for osteoporosis remains undiscovered. Here, we investigated whether Iso might suppress the differentiation of osteoclasts in vitro and in vivo to play an anti-osteoporosis role. Our results showed that Iso inhibits the formation of mature multinuclear osteoclasts induced by RANKL, the bone resorption, and the osteoclast-specific genes expression by blocking the nuclear translocation of NF-κB p65, and the effect was in a dosage-dependent way. Furthermore, we investigated the therapeutic effect of Iso on osteoporosis in ovariectomized (OVX) mice. We found that Iso attenuated bone loss in the OVX mice and significantly promoted BS, Conn. DN, Tb.Th, TB.N, and BV/TV Index. All in all, Iso showed a prominent effect of osteoclast inhibition, with great promise for treating osteoporosis.

Keywords: NF-κB pathway; isoliensinine; osteoclast; osteoporosis; receptor activator of nuclear factor-κB ligand (RANKL).