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AN698/40746067 suppresses bone marrow adiposity to ameliorate hyperlipidemia-induced osteoporosis through targeted inhibition of ENTR1.
Ren, Huiping; Mao, Kai; Yuan, Xin; Mu, Yuqing; Zhao, Shuaiqi; Fan, Xin; Zhu, Lina; Ye, Zhou; Lan, Jing.
Afiliação
  • Ren H; Department of Prosthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical
  • Mao K; Department of Prosthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical
  • Yuan X; Department of Prosthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical
  • Mu Y; Department of Prosthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical
  • Zhao S; Department of Prosthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical
  • Fan X; Department of Stomatology, Affiliated Hospital of Weifang Medical University, 261053 China.
  • Zhu L; Department of Pediatric Dentistry, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University, Shandong Key Laboratory of Oral Tissue Regeneration, Shandong Engineering Laboratory for Dental Materials and Oral Tissue Regeneration, Jinan 250012, China.
  • Ye Z; Applied Oral Sciences and Community Dental Care, Faculty of Dentistry, The University of Hong Kong, 999077, Hong Kong Special Administrative Region of China.
  • Lan J; Department of Prosthodontics, School and Hospital of Stomatology, Cheeloo College of Medicine, Shandong University & Shandong Key Laboratory of Oral Tissue Regeneration & Shandong Engineering Research Center of Dental Materials and Oral Tissue Regeneration & Shandong Provincial Clinical
Biomed Pharmacother ; 176: 116843, 2024 Jul.
Article em En | MEDLINE | ID: mdl-38810405
ABSTRACT
Hyperlipidemia-induced osteoporosis is marked by increased bone marrow adiposity, and treatment with statins for hyperlipidemia often leads to new-onset osteoporosis. Endosome-associated trafficking regulator 1 (ENTR1) has been found to interact with different proteins in pathophysiology, but its exact role in adipogenesis is not yet understood. This research aimed to explore the role of ENTR1 in adipogenesis and to discover a new small molecule that targets ENTR1 for evaluating its effectiveness in treating hyperlipidemia-induced osteoporosis. We found that ENTR1 expression increased during the adipogenesis of bone marrow mesenchymal cells (BMSCs). ENTR1 gain- and loss-of-function assays significantly enhanced lipid droplets formation. Mechanistically, ENTR1 binds peroxisome proliferator-activated receptor γ (PPARγ) and enhances its expression, thereby elevating adipogenic markers including C/EBPα and LDLR. Therapeutically, AN698/40746067 attenuated adipogenesis by targeting ENTR1 to suppress PPARγ. In vivo, AN698/40746067 reduced bone marrow adiposity and bone loss, as well as prevented lipogenesis-related obesity, inflammation, steatohepatitis, and abnormal serum lipid levels during hyperlipidemia. Together, these findings suggest that ENTR1 facilitates adipogenesis by PPARγ involved in BMSCs' differentiation, and targeted inhibition of ENTR1 by AN698/40746067 may offer a promising therapy for addressing lipogenesis-related challenges and alleviating osteoporosis following hyperlipidemia.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Osteoporose / Medula Óssea / PPAR gama / Adipogenia / Células-Tronco Mesenquimais / Hiperlipidemias Limite: Animals Idioma: En Revista: Biomed Pharmacother Ano de publicação: 2024 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Osteoporose / Medula Óssea / PPAR gama / Adipogenia / Células-Tronco Mesenquimais / Hiperlipidemias Limite: Animals Idioma: En Revista: Biomed Pharmacother Ano de publicação: 2024 Tipo de documento: Article