Dancr-BRG1 regulates Nfatc1 transcription and Pgc1β-dependent metabolic shifts in osteoclastogenesis.
Zheng ZhangYichen MengTao LinZhanrong ZhangZhengbo TaoHao-Zan YinFu YangXuhui ZhouPublished in: Proceedings of the National Academy of Sciences of the United States of America (2024)
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.
Keyphrases
- bone loss
- long non coding rna
- bone mineral density
- poor prognosis
- nuclear factor
- transcription factor
- postmenopausal women
- public health
- toll like receptor
- binding protein
- genome wide
- sars cov
- skeletal muscle
- cell proliferation
- inflammatory response
- genome wide identification
- oxidative stress
- high glucose
- metabolic syndrome
- endothelial cells
- climate change
- amino acid
- replacement therapy
- insulin resistance