DNA damage-inducible transcript 3 restrains osteoclast differentiation and function

Yang, Bin; Sun, Hairong; Jia, Meie; He, Ying; Luo, Yao; Wang, Tianqi; Wu, Yanru; Wang, Jiawei

doi:10.1016/j.bone.2021.116162

Cited by 7 publications

(12 citation statements)

References 44 publications

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“…The prevention of alveolar bone resorption is a crucial clinical challenge in periodontitis treatment. Our previous study showed that 8‐week‐old DDIT3 KO mice exhibited a modest decrease in femur bone mass 14 . Here, micro‐CT scanning and stereoscopic microscopy revealed that DDIT3 KO mice displayed more alveolar bone resorption compared with WT mice after 8 days of ligature.…”

Section: Discussionmentioning

confidence: 53%

“…Because we could not extract enough RNA from one mouse sample, samples from three to four mice were put together for RNA extraction (9–24 mice for each group). qRT‐PCR was conducted as previously described 14 . The expression of the following markers was determined: DDIT3, TNF‐α, IL‐1β, IL‐6, CTSK, dendritic cell‐specific transmembrane protein (DC‐STAMP), TRAP, and nuclear factor of activated T cells cytoplasmic 1 (NFATc1).…”

Section: Methodsmentioning

confidence: 99%

“…Bone marrow cells were extracted from the tibias and femurs of 8‐week‐old wild‐type or DDIT3 knockout mice as previously described 14 . The cells were cultured with α‐minimal essential medium (α‐MEM, Hyclone) with 10% fetal bovine serum (CellMax) and macrophage colony‐stimulating factor (20 ng/mL M‐CSF, Peprotech) for 3 days to recruit osteoclast precursors BMMs.…”

Section: Methodsmentioning

confidence: 99%

“…DDIT3 inhibits adipocyte differentiation, but its roles in the regulation of osteogenic differentiation remain controversial 11–13 . DDIT3 negatively regulates the differentiation of osteoclast by suppressing cathepsin K (CTSK) expression 14 . DDIT3 also suppresses cementoblast mineralization 15 .…”

Section: Introductionmentioning

confidence: 99%

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DNA damage‐inducible transcript 3 deficiency promotes bone resorption in murine periodontitis models

Luo

Yang

Dong

et al. 2023

J of Periodontal Research

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Background and Objective: Periodontitis is a multifactorial inflammatory disease that leads to the destruction of supporting structures of the teeth. DNA damage-inducible transcript 3 (DDIT3) plays crucial roles in cell survival and differentiation. DDIT3 regulates bone mass and osteoclastogenesis in femur. However, the role of DDIT3 in periodontitis has not been elucidated. This research aimed to explore the role and mechanisms of DDIT3 in periodontitis.Methods: DDIT3 gene knockout (KO) mice were generated using a CRISPR/Cas9 system. Experimental periodontitis models were established to explore the role of DDIT3 in periodontitis. The expression of DDIT3 in periodontal tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR) and immunohistochemistry (IHC). The alveolar bone phenotypes were observed by micro-CT and stereomicroscopy. The inflammation levels and osteoclast activity were examined by histological staining, immunostaining, and qRT-PCR. Bone marrow-derived macrophages (BMMs) were isolated to confirm the effects of DDIT3 on osteoclast formation and function in vitro. Results:The increased expression of DDIT3 in murine inflamed periodontal tissues was detected. DDIT3 knockout aggravated alveolar bone loss and enhanced expression levels of inflammatory cytokines in murine periodontitis models. Increased osteoclast formation and higher expression levels of osteoclast-specific markers were observed in the inflamed periodontal tissues of KO mice. In vitro, DDIT3 deficiency promoted the formation of tartrate-resistant acid phosphatase (TRAP)-positive multinucleated osteoclasts and the bone resorption activity of mature osteoclasts. Conclusions:Our results demonstrate that DDIT3 deletion aggravated alveolar bone loss in experimental periodontitis through enhanced inflammatory reactions and osteoclastogenesis. The anti-inflammation and the inhibition of bone loss by DDIT3 in murine periodontitis provides a potential novel therapeutic strategy for periodontitis.

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Section: Discussionmentioning

confidence: 53%

Section: Methodsmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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DNA damage‐inducible transcript 3 deficiency promotes bone resorption in murine periodontitis models

Luo

Yang

Dong

et al. 2023

J of Periodontal Research

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show abstract

“…Finally, we highlight the TF DDIT3 , which was already associated with osteoclastogenesis. Its absence enhances osteoclast formation and aggravation of bone resorption, a hallmark in osteoarthritic subchondral bone [ 50 ]. We found that this gene is exclusive to the apoptosis osteoarthritis network, indicating that DDIT3 might play an important role in the cartilage-to-bone transition.…”

Section: Discussionmentioning

confidence: 99%

Differential gene co-expression network analyses reveal novel molecules associated with transcriptional dysregulation of key biological processes in osteoarthritis knee cartilage

Buzzatto-Leite

Afonso

Silva-Vignato

et al. 2022

Osteoarthritis and Cartilage Open

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DDIT3 deficiency accelerates bone remodeling during bone healing by enhancing osteoblast and osteoclast differentiation through ULK1-mediated autophagy

Jia,

Dong,

Dong

et al. 2024

Bone

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DNA damage-inducible transcript 3 restrains osteoclast differentiation and function

Cited by 7 publications

References 44 publications

DNA damage‐inducible transcript 3 deficiency promotes bone resorption in murine periodontitis models

DNA damage‐inducible transcript 3 deficiency promotes bone resorption in murine periodontitis models

Differential gene co-expression network analyses reveal novel molecules associated with transcriptional dysregulation of key biological processes in osteoarthritis knee cartilage

DDIT3 deficiency accelerates bone remodeling during bone healing by enhancing osteoblast and osteoclast differentiation through ULK1-mediated autophagy

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