SREBP2 restricts osteoclast differentiation and activity by regulating IRF7 and limits inflammatory bone erosion.

Autor: Kim H; Arthritis and Tissue Degeneration Program, David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY, 11366, USA.; Department of Medicine, Weill Cornell Medical College, New York, NY, 10021, USA.; CHA Biomedical Research Institute, CHA Bundang Medical Center, CHA University School of Medicine, Seongnam, 13496, Republic of Korea., Choi IA; Arthritis and Tissue Degeneration Program, David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY, 11366, USA.; Department of Internal Medicine, College of Medicine, Chungbuk National University, Cheongju, Chungbuk, 28644, Republic of Korea., Umemoto A; Arthritis and Tissue Degeneration Program, David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY, 11366, USA., Bae S; Arthritis and Tissue Degeneration Program, David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY, 11366, USA.; Department of Medicine, Weill Cornell Medical College, New York, NY, 10021, USA., Kaneko K; Arthritis and Tissue Degeneration Program, David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY, 11366, USA., Mizuno M; Arthritis and Tissue Degeneration Program, David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY, 11366, USA., Giannopoulou E; Arthritis and Tissue Degeneration Program, David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY, 11366, USA.; Biological Sciences Department, New York City College of Technology, City University of New York, Brooklyn, NY, 11201, USA., Pannellini T; Arthritis and Tissue Degeneration Program, David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY, 11366, USA., Deng L; Dermatology Service, Department of Medicine, Memorial Sloan Kettering Cancer Center, New York, NY, 10065, USA.; Department of Dermatology, Weill Cornell Medical College, New York, NY, 10021, USA., Park-Min KH; Arthritis and Tissue Degeneration Program, David Z. Rosensweig Genomics Research Center, Hospital for Special Surgery, New York, NY, 11366, USA. ParkminK@hss.edu.; Department of Medicine, Weill Cornell Medical College, New York, NY, 10021, USA. ParkminK@hss.edu.; BCMB Allied Program, Weill Cornell Graduate School of Medical Sciences, New York, NY, 10065, USA. ParkminK@hss.edu.
Jazyk: angličtina
Zdroj: Bone research [Bone Res] 2024 Aug 27; Vol. 12 (1), pp. 48. Date of Electronic Publication: 2024 Aug 27.
DOI: 10.1038/s41413-024-00354-4
Abstrakt: Osteoclasts are multinucleated bone-resorbing cells, and their formation is tightly regulated to prevent excessive bone loss. However, the mechanisms by which osteoclast formation is restricted remain incompletely determined. Here, we found that sterol regulatory element binding protein 2 (SREBP2) functions as a negative regulator of osteoclast formation and inflammatory bone loss. Cholesterols and SREBP2, a key transcription factor for cholesterol biosynthesis, increased in the late phase of osteoclastogenesis. The ablation of SREBP2 in myeloid cells resulted in increased in vivo and in vitro osteoclastogenesis, leading to low bone mass. Moreover, deletion of SREBP2 accelerated inflammatory bone destruction in murine inflammatory osteolysis and arthritis models. SREBP2-mediated regulation of osteoclastogenesis is independent of its canonical function in cholesterol biosynthesis but is mediated, in part, by its downstream target, interferon regulatory factor 7 (IRF7). Taken together, our study highlights a previously undescribed role of the SREBP2-IRF7 regulatory circuit as a negative feedback loop in osteoclast differentiation and represents a novel mechanism to restrain pathological bone destruction.
(© 2024. The Author(s).)
Databáze: MEDLINE
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