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SOD3 regulates FLT1 to affect bone metabolism by promoting osteogenesis and inhibiting adipogenesis through PI3K/AKT and MAPK pathways.
Xu, Ke; Fei, Wenchao; Gao, Wenxue; Fan, Changxiu; Li, Yinghua; Hong, Yang; Cui, Ran.
Afiliación
  • Xu K; Department of Orthopedics, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China; Shanghai Clinical Research Center for Aging and Medicine, Shanghai, China; Center of Community-Based Health Research, Fudan University, Shanghai, China. Electronic address: 21111290003@m.fudan.edu.
  • Fei W; Department of Orthopedics, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China; Shanghai Clinical Research Center for Aging and Medicine, Shanghai, China; Center of Community-Based Health Research, Fudan University, Shanghai, China. Electronic address: feiwenchao@fudan.edu.cn.
  • Gao W; Medical Services Section, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address: gaowx2000@163.com.
  • Fan C; Department of Stomatology, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China. Electronic address: fancx1996119@foxmail.com.
  • Li Y; Shanghai Clinical Research Center for Aging and Medicine, Shanghai, China; Center of Community-Based Health Research, Fudan University, Shanghai, China; Central Laboratory, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China. Electronic address: zhulihan@fudan.edu.cn.
  • Hong Y; Department of Orthopedics, The Fifth People's Hospital of Shanghai, Fudan University, Shanghai, China; Shanghai Clinical Research Center for Aging and Medicine, Shanghai, China; Center of Community-Based Health Research, Fudan University, Shanghai, China. Electronic address: hongyangcm@163.com.
  • Cui R; Department of Endocrinology and Metabolism, Shanghai Tenth People's Hospital, Tongji University School of Medicine, Shanghai, China. Electronic address: cuiran1172@163.com.
Free Radic Biol Med ; 212: 65-79, 2024 02 20.
Article en En | MEDLINE | ID: mdl-38141889
ABSTRACT
Osteoporosis is a chronic disease that seriously affects the quality of life and longevity of the elderly, so exploring the mechanism of osteoporosis is crucial for drug development and treatment. Bone marrow mesenchymal stem cells are stem cells with multiple differentiation potentials in bone marrow, and changing their differentiation direction can change bone mass. As an extracellular superoxide dismutase, Superoxide Dismutase 3 (SOD3) has been proved to play an important role in multiple organs, but the detailed mechanism of action in bone metabolism is still unclear. In this study, the results of clinical serum samples ELISA and single cell sequencing chip analysis proved that the expression of SOD3 was positively correlated with bone mass, and SOD3 was mainly expressed in osteoblasts and adipocytes and rarely expressed in osteoblasts in BMSCs. In vitro experiments showed that SOD3 can promote osteogenesis and inhibit adipogenesis. Compared with WT mice, the mice that were knocked out of SOD3 had a significant decrease in bone mineral density and significant changes in related parameters. The results of HE and IHC staining suggested that knocking out SOD3 would lead to fat accumulation in the bone marrow cavity and weakened osteogenesis. Both in vitro and in vivo experiments indicated that SOD3 affects bone metabolism by promoting osteogenesis and inhibiting adipogenesis. The results of transcriptome sequencing and revalidation showed that SOD3 can affect the expression of FLT1. Through in vitro experiments, we proved that FLT1 can also promote osteogenesis and inhibit adipogenesis. In addition, through the repeated experiments, the interaction between the two molecules (SOD3 and FLT1) was verified again. Finally, it was verified by WB that SOD3 regulates FLT1 to affect bone metabolism through PI3K/AKT and MAPK pathways.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoporosis / Adipogénesis Límite: Aged / Animals / Humans Idioma: En Revista: Free Radic Biol Med Asunto de la revista: BIOQUIMICA / MEDICINA Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteoporosis / Adipogénesis Límite: Aged / Animals / Humans Idioma: En Revista: Free Radic Biol Med Asunto de la revista: BIOQUIMICA / MEDICINA Año: 2024 Tipo del documento: Article Pais de publicación: Estados Unidos