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Inhibition of FAAH suppresses RANKL-induced osteoclastogenesis and attenuates ovariectomy-induced bone loss partially through repressing the IL17 pathway.
Zhu, Meipeng; Guo, Qian; Kang, Honglei; Peng, Renpeng; Dong, Yimin; Zhang, Yayun; Wang, Sibo; Liu, Haiyang; Zhao, Hongjian; Dong, Zijian; Song, Kehan; Xu, Shimeng; Wang, Pengju; Chen, Liangxi; Liu, Jian; Li, Feng.
Afiliación
  • Zhu M; Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Guo Q; Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Kang H; Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Peng R; Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Dong Y; Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Zhang Y; Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Wang S; Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Liu H; Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Zhao H; Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Dong Z; Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Song K; Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Xu S; Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Wang P; Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Chen L; Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Liu J; Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
  • Li F; Department of Orthopedics, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
FASEB J ; 37(1): e22690, 2023 01.
Article en En | MEDLINE | ID: mdl-36468880
Fatty amide hydrolase (FAAH) is a key degradation enzyme of the endocannabinoid system, mainly responsible for the hydrolysis of arachidonic acid ethanolamine (AEA). Previous investigations have shown that FAAH is involved in a series of biological processes, such as inflammation, immune regulation, and transmembrane signal transduction of neurons. Endogenous cannabinoids and cannabinoid receptors have been reported to participate in the regulation of bone homeostasis by regulating the differentiation of osteoblasts and osteoclasts. We hypothesized that FAAH may play an important role in osteoclastogenesis based on the above evidence. The present study found that the FAAH expression was increased at both mRNA and protein levels during RANKL-induced osteoclastogenesis. Pharmacological and genetic inhibition of FAAH in bone marrow-derived macrophages (BMMs) inhibited osteoclastogenesis, F-actin ring formation, bone resorption, and osteoclast-specific gene expression in vitro. Moreover, intragastric administration of the FAAH inhibitor PF-04457845(PF) ameliorated ovariectomy (OVX)-induced bone loss in mice. Further investigation revealed that nuclear factor κB (NF-κB) and mitogen-activated protein kinase (MAPK) pathways were inhibited by PF treatment and FAAH knockdown. RNAseq indicated that the IL17 pathway was blocked by PF, and administration of recombinant murine IL17 protein could partially restore osteoclastogenesis and activate NF-κB and MAPK pathways. To sum up, our findings demonstrate that targeting FAAH could be a promising candidate strategy for treating osteoclast-related diseases, especially osteoporosis.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteogénesis / Resorción Ósea / Interleucina-17 / Amidohidrolasas Tipo de estudio: Etiology_studies Límite: Animals Idioma: En Revista: FASEB J Asunto de la revista: BIOLOGIA / FISIOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Osteogénesis / Resorción Ósea / Interleucina-17 / Amidohidrolasas Tipo de estudio: Etiology_studies Límite: Animals Idioma: En Revista: FASEB J Asunto de la revista: BIOLOGIA / FISIOLOGIA Año: 2023 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos