Osteoporosis deteriorates bone mass and biomechanical strength and is life-threatening to the elderly.In this study,we show that methyl 3,4-dihydroxybenzoate(MDHB),an antioxidant small-molecule compound extracted from natural plants,inhibits receptor activator of nuclear factor-кB(NF-кB)ligand(RANKL)-induced osteoclastogenesis in vitro.Furthermore,MDHB attenuates the activation of mitogen-activated protein kinase(MAPK)and NF-κB path-ways by reducing the levels of reactive oxygen species(ROS),which leads to downregulated protein expression of c-Fos and nuclear factor of activated T cells c1(NFATc1).We also confirm that MDHB upregulates the protein expression of nuclear factor-erythroid 2-related factor 2(Nrf2),an important transcription factor involved in ROS regulation,by inhibiting the ubiquitination-mediated proteasomal degradation of Nrf2.Next,animal experiments show that MDHB has an effective therapeutic effect on lipopolysaccharide(LPS)-and ovariectomized(OVX)-induced bone loss in mice.Our study demonstrates that MDHB can upregulate Nrf2 and suppress excessive osteoclast activity in mice to treat osteoporosis.

Zhaobo Huang;Zenghui Jiang;Zeyu Zheng;Xuyang Zhang;Xiaoan Wei;Jian Chen;Fengdong Zhao

Department of Orthopaedics,Sir Run Run Shaw Hospital,Zhejiang University School of Medicine,Hangzhou 310016 China;Key Laboratory of Musculoskeletal System Degeneration and Regeneration Translational Research of Zhejiang Province,Hangzhou 310016,China;Department of Orthopaedics,Xia Sha Hospital of Hangzhou City,Hangzhou 310018,China;Department of Orthopaedic Surgery,Zhejiang Hospital,Hangzhou 310030,China

生物化学与生物物理学报（英文版）

[1]Zhaobo Huang;Zenghui Jiang;Zeyu Zheng;Xuyang Zhang;Xiaoan Wei;Jian Chen;Fengdong Zhao-.Methyl 3,4-dihydroxybenzoate inhibits RANKL-induced osteoclastogenesis via Nrf2 signaling in vitro and suppresses LPS-induced osteolysis and ovariectomy-induced osteoporosis in vivo)[J].生物化学与生物物理学报（英文版）,2022(08):1068-1079

dihydroxybenzoate,MDHB

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