Dancr-BRG1 regulates Nfatc1 transcription and Pgc1β-dependent metabolic shifts in osteoclastogenesis.

Autor:	Zhang Z; Department of Orthopedics, Changzheng Hospital, Second Military Medical University (Naval Medical University), Shanghai 200003, China.; Department of Orthopedic rehabilitation, Qingdao Special Servicemen Recuperation Center of People's Liberation Army Navy, Qingdao 266000, China., Meng Y; Department of Orthopedics, Changzheng Hospital, Second Military Medical University (Naval Medical University), Shanghai 200003, China., Lin T; Department of Orthopedics, Changzheng Hospital, Second Military Medical University (Naval Medical University), Shanghai 200003, China., Zhang Z; Department of Orthopedics, Changzheng Hospital, Second Military Medical University (Naval Medical University), Shanghai 200003, China., Tao Z; Department of Orthopedics, Changzheng Hospital, Second Military Medical University (Naval Medical University), Shanghai 200003, China., Yin H; Department of Medical Genetics, Second Military Medical University (Naval Medical University), Shanghai 200433, China., Yang F; Department of Medical Genetics, Second Military Medical University (Naval Medical University), Shanghai 200433, China.; Key Laboratory of Biological Defense, Ministry of Education, Shanghai 200433, China., Zhou X; Department of Orthopedics, Changzheng Hospital, Second Military Medical University (Naval Medical University), Shanghai 200003, China.; Translational research center of orthopedics, Shanghai General Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 201600, China.
Jazyk:	angličtina
Zdroj:	Proceedings of the National Academy of Sciences of the United States of America [Proc Natl Acad Sci U S A] 2024 Jan 30; Vol. 121 (5), pp. e2313656121. Date of Electronic Publication: 2024 Jan 22.
DOI:	10.1073/pnas.2313656121
Abstrakt:	Long non-coding RNA (lncRNA) serves as a vital regulator of bone metabolism, but its role in pathologically overactive osteoclast differentiation remains elusive. Here, we identify lncRNA Dancr (Differentiation Antagonizing Non-protein Coding RNA) as a critical suppressor of osteoclastogenesis and bone resorption, which is down-regulated in response to estrogen deficiency. Global or osteoclast-specific Dancr Knockout mice display significant trabecular bone deterioration and enhanced osteoclast activity, but minimal alteration of bone formation. Moreover, the bone-targeted delivery of Dancr by Adeno-associated viral remarkably attenuates ovariectomy-induced osteopenia in mice. Mechanistically, Dancr establishes a direct interaction with Brahma-related gene 1 to prevent its binding and preserve H3K27me3 enrichment at the nuclear factor of activated T cells 1 and proliferator-activated receptor gamma coactivator 1-beta promoters, thereby maintaining appropriate expression of osteoclastic genes and metabolic programs during osteoclastogenesis. These results demonstrate that Dancr is a key molecule maintaining proper osteoclast differentiation and bone homeostasis under physiological conditions, and Dancr overexpression constitutes a potential strategy for treating osteoporosis. Competing Interests: Competing interests statement:The authors declare no competing interest.
Databáze:	MEDLINE
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