DNA methyltransferases inhibitor azacitidine improves the skeletal phenotype of mild osteogenesis imperfecta by reversing the impaired osteogenesis and excessive osteoclastogenesis

Shao, Chenyi; Liu, Yi; Zhao, Yijiao; Jing, Yaqing; Li, Jiaci; Lv, Zhe; Fu, Ting; Wang, Zihan; Li, Guang

doi:10.1016/j.bone.2023.116706

Cited by 3 publications

(2 citation statements)

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“…Fam210a global knockout in mice induced in utero death of the embryos and decreased bone mineral density and bone biomechanical strength (Tanaka et al, 2018). Consistently, several reports showed that cold exposure affects the DNA methylation of osteogenic genes and bone development (Robbins et al, 2018;Shao et al, 2023). Therefore, the presence of altered methylation levels in all these genes in sperm might potentially impact osteogenesis in offspring.…”

Section: Discussionmentioning

confidence: 80%

Cold exposure impacts DNA methylation patterns in cattle sperm

Hossain,

Gao,

Hatfield

et al. 2024

Front. Genet.

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DNA methylation is influenced by various exogenous factors such as nutrition, temperature, toxicants, and stress. Bulls from the Pacific Northwest region of the United States and other northern areas are exposed to extreme cold temperatures during winter. However, the effects of cold exposure on the methylation patterns of bovine sperm remain unclear. To address, DNA methylation profiles of sperm collected during late spring and winter from the same bulls were analyzed using whole genome bisulfite sequencing (WGBS). Bismark (0.22.3) were used for mapping the WGBS reads and R Bioconductor package DSS was used for differential methylation analysis. Cold exposure induced 3,163 differentially methylated cytosines (DMCs) with methylation difference ≥10% and a q-value < 0.05. We identified 438 differentially methylated regions (DMRs) with q-value < 0.05, which overlapped with 186 unique genes. We also identified eight unique differentially methylated genes (DMGs) (Pax6, Macf1, Mest, Ubqln1, Smg9, Ctnnb1, Lsm4, and Peg10) involved in embryonic development, and nine unique DMGs (Prmt6, Nipal1, C21h15orf40, Slc37a3, Fam210a, Raly, Rgs3, Lmbr1, and Gan) involved in osteogenesis. Peg10 and Mest, two paternally expressed imprinted genes, exhibited >50% higher methylation. The differential methylation patterns of six distinct DMRs: Peg10, Smg9 and Mest related to embryonic development and Lmbr1, C21h15orf40 and Prtm6 related to osteogenesis, were assessed by methylation-specific PCR (MS-PCR), which confirmed the existence of variable methylation patterns in those locations across the two seasons. In summary, cold exposure induces differential DNA methylation patterns in genes that appear to affect embryonic development and osteogenesis in the offspring. Our findings suggest the importance of replicating the results of the current study with a larger sample size and exploring the potential of these changes in affecting offspring development.

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Section: Discussionmentioning

confidence: 80%

Cold exposure impacts DNA methylation patterns in cattle sperm

Hossain,

Gao,

Hatfield

et al. 2024

Front. Genet.

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“…MSCs derived from the subchondral bone of the rat condyle (SMSCs) have higher expression of DNMT3B and significantly higher mineralization and osteogenic differentiation potential compared to MSCs derived from the tibia (TMSCs) and mandibular ramus bone marrow (MMSCs) ( Wang Y. et al, 2023 ). Osteogenesis imperfecta (OI) mice with ADSCs express high levels of DNMT3A compared to wild-type mice with ADSCs, and their osteogenic differentiation ability and collagen secretion are significantly impaired ( Shao et al, 2023 ). Differentially expressed DNMTs may reflect the differences in epigenetic regulation between different subgroups of MSCs, and this regulation may be one of the key factors in maintaining the characteristics of different MSCs subgroups.…”

Section: The Role Of Dnmts In Osteogenic Differentiation Of Mscsmentioning

confidence: 99%

Effect of DNA methylation on the osteogenic differentiation of mesenchymal stem cells: concise review

Lai,

Shu,

Song

et al. 2024

Front. Genet.

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Mesenchymal stem cells (MSCs) have promising potential for bone tissue engineering in bone healing and regeneration. They are regarded as such due to their capacity for self-renewal, multiple differentiation, and their ability to modulate the immune response. However, changes in the molecular pathways and transcription factors of MSCs in osteogenesis can lead to bone defects and metabolic bone diseases. DNA methylation is an epigenetic process that plays an important role in the osteogenic differentiation of MSCs by regulating gene expression. An increasing number of studies have demonstrated the significance of DNA methyltransferases (DNMTs), Ten-eleven translocation family proteins (TETs), and MSCs signaling pathways about osteogenic differentiation in MSCs. This review focuses on the progress of research in these areas.

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