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Puerarin alleviates osteoporosis in the ovariectomy-induced mice by suppressing osteoclastogenesis via inhibition of TRAF6/ROS-dependent MAPK/NF-?B signaling pathways.

ABSTRACT: In this study, we investigated the mechanisms by which puerarin alleviates osteoclast-related loss of bone mass in ovariectomy (OVX)-induced osteoporosis model mice. Puerarin-treated OVX mice exhibited higher bone density, fewer tartrate-resistant acid phosphatase (TRAcP)-positive osteoclasts, and levels of lower reactive oxygen species (ROS) within bone tissues than vehicle-treated OVX mice. Puerarin suppressed in vitro osteoclast differentiation, hydroxyapatite resorption activity, and expression of osteoclastogenesis-related genes, such as NFATc1, MMP9, CTSK, Acp5 and c-Fos, in RANKL-induced bone marrow macrophages (BMMs) and RAW264.7 cells. It also reduced intracellular ROS levels by suppressing expression of TRAF6 and NADPH oxidase 1 (NOX1) and increasing expression of antioxidant enzymes such as heme oxygenase-1 (HO-1). Puerarin inhibited TRAF6/ROS-dependent activation of the MAPK and NF-?B signaling pathways in RANKL-induced RAW264.7 cells, and these effects were partially reversed by HO-1 silencing or TRAF6 overexpression. These findings suggest puerarin alleviates loss of bone mass in the OVX-model mice by suppressing osteoclastogenesis via inhibition of the TRAF6/ROS-dependent MAPK/NF-?B signaling pathway.

SUBMITTER: Xiao L

PROVIDER: S-EPMC7695364 | biostudies-literature | 2020 Nov

REPOSITORIES: biostudies-literature

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Puerarin alleviates osteoporosis in the ovariectomy-induced mice by suppressing osteoclastogenesis via inhibition of TRAF6/ROS-dependent MAPK/NF-κB signaling pathways.

Xiao Long L Zhong Mengdan M Huang Yu Y Zhu Jie J Tang Wenkai W Li Danyong D Shi Jiandong J Lu Aiqing A Yang Huilin H Geng Dechun D Li Hong H Wang Zhirong Z

Aging 20201107 21

In this study, we investigated the mechanisms by which puerarin alleviates osteoclast-related loss of bone mass in ovariectomy (OVX)-induced osteoporosis model mice. Puerarin-treated OVX mice exhibited higher bone density, fewer tartrate-resistant acid phosphatase (TRAcP)-positive osteoclasts, and levels of lower reactive oxygen species (ROS) within bone tissues than vehicle-treated OVX mice. Puerarin suppressed <i>in vitro</i> osteoclast differentiation, hydroxyapatite resorption activity, and ...[more]

PMID: 33176281

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Project description:Acute lung injury (ALI) induced by paraquat (PQ) progresses rapidly with high mortality; however, there is no effective treatment, and the specific mechanism is not well understood. The antiaging protein klotho (KL) has multiple functions and exerts significant influences on various pathophysiological processes. This work evaluated the impact of KL on PQ-induced ALI and investigated its underlying mechanisms. As for in vivo research, C57BL/6 mice were treated with PQ (30?mg/kg) intraperitoneal (IP) injection to create a toxicity model of ALI (PQ group). The mice were divided into control group, KL group, PQ group, and PQ+KL group. For in vitro experiment, A549 cells were incubated with or without KL and then treated in the presence or absence of PQ for 24?h. In vivo result indicated that KL reduced the mortality, reduced IL-1? and IL-6 in the bronchoalveolar lavage fluid (BALF), attenuated ALI, and decreased apoptosis in situ. In vitro result revealed that KL significantly improved cell viability, reduced the levels of IL-1? and IL-6 in culture supernatants, suppressed cell apoptosis, inhibited caspase-3 activation, and enhanced mitochondrial membrane potential (??m) after PQ treatment. Besides, KL effectively abated reactive oxygen species (ROS) production, improved GSH content, and lowered lipid peroxidation in PQ-exposed A549 cells. Further experiments indicated that phosphorylated JNK and P38 MAPK was increased after PQ treatment; however, KL pretreatment could significantly lower the phosphorylation of P38 MAPK. Suppression of P38 MAPK improved cell viability, alleviated inflammatory response, and reduced apoptosis-related signals; however, it had no obvious effect on the production of ROS. Treatment with N-acetylcysteine (NAC), a classic ROS scavenger, could suppress ROS production and P38 MAPK activation. These findings suggested that KL could alleviate PQ-caused ALI via inhibiting ROS/P38 MAPK signaling-regulated inflammatory responses and mitochondria-dependent apoptosis.

Dataset Information

Puerarin alleviates osteoporosis in the ovariectomy-induced mice by suppressing osteoclastogenesis via inhibition of TRAF6/ROS-dependent MAPK/NF-?B signaling pathways.

Publications

Puerarin alleviates osteoporosis in the ovariectomy-induced mice by suppressing osteoclastogenesis via inhibition of TRAF6/ROS-dependent MAPK/NF-κB signaling pathways.

Similar Datasets

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