Zhuo Wang,Weixiao Nan,Huazhe Si,Shiyong Wang,Haihua Zhang,Guangyu Li
Aims Pantothenic acid (PA) has been applied to treat alopecia, but the underlying mechanism is still unclear. Our study aims to explore the underlying mechanism of PA in regulating hair follicle (HF) growth. Main methods Mink HFs and dermal papilla (DP) cells were isolated and cultured in vitro . HFs and DP cells were treated with 0, 10, 20, 40 μg/ml PA. The effect of PA on HF growth, DP cell proliferation, cell cycle distribution, cell migration, and insulin-like growth factor-1 (IGF-1) and vascular endothelial growth factor (VEGF) expressions in DP cells was measured. Moreover, the effect of PA on inhibitor of DNA binding 3 (ID3)/Notch signaling pathway was analyzed. Subsequently, ID3 was silenced to validate whether ID3/Notch signaling pathway was involved in regulating DP cell proliferation by PA. Key findings Both 20 μg/ml and 40 μg/ml PA promoted HF growth, G1/S transition of DP cells and IGF-1 and VEGF expressions in DP cells, while only 20 μg/ml PA promoted cell viability and the migration of DP cells. Thus 20 μg/ml PA was chosen for the following experiments. PA treatment was found to up-regulate ID3 expression but down-regulate Notch receptor 1 (Notch1) and Notch signaling targets expressions. Furthermore, ID3 knockdown reversed PA-induced cell proliferation and inhibition of Notch1 and Notch signaling targets expressions, indicating that PA-induced DP cell proliferation and inhibition of Notch signaling were mediated via up-regulation of ID3. Significance This study provides an underlying mechanism related to the effect of PA on stimulating DP cell proliferation.
Aoran Huang,Jianyun Rao,Xin Feng,Xingru Li,Tianhua Xu,Li Yao
Vascular calcification (VC) poses significant challenges in cardiovascular health. This study employs single-cell transcriptome sequencing to dissect cellular dynamics in this process. We identify distinct cell subgroups, notably in vascular smooth muscle cells (VSMCs), and observe differences between calcified atherosclerotic cores and adjacent regions. Further exploration reveals ID3 as a key gene regulating VSMC function. In vitro experiments demonstrate ID3′s interaction with USP1 and E12, modulating cell proliferation and osteogenic differentiation. Animal models confirm the critical role of the USP1/ID3/E12/P21 axis in VC. This study sheds light on a novel regulatory mechanism, offering potential therapeutic targets. 1. This study uses single-cell transcriptome to investigate vascular calcification in depth. 2. This study successfully identifies cellular heterogeneity related to vascular calcification. 3. This study reveals the crucial role of ID3 in vascular smooth muscle cell osteogenic differentiation. 4. In vivo and in vitro experiments of this study demonstrate the regulatory role of the USP1/ID3/E12/P21 axis in calcification. 5. This study provides potential molecular targets for the treatment of calcification-related diseases.
Jie Chen,Yiwei Zhao,Chongmai Zeng,Guoli Tian,Zhicai Feng,Yang Cao
Background Craniomaxillofacial sutures play a critical role in craniomaxillofacial development through continuous bone reconstruction and regeneration, processes modulated by mechanical tension. Bone suture stem cells (SuSCs) are central to these functions. Distraction osteogenesis, which promotes craniomaxillofacial suture growth, is a common therapeutic approach for craniofacial deformities. However, the underlying mechanisms by which mechanical forces drive suture and bone remodeling remain poorly understood, posing significant clinical challenges. Methods To investigate these mechanisms, we established a rapid maxillary expansion (RME) model in mice to widen the midpalatal suture. Single-cell RNA sequencing (scRNA-seq) was employed to identify subsets of SuSCs responsive to mechanical tension and analyze their differentiation potential under varying conditions. Further functional studies were conducted to explore the role of DALR anticodon binding domain containing 3 (Dalrd3) and its associated tRNA 3-methylcytosine (m3C) modification in SuSCs under mechanical tension. Results Our study identified a subset of SuSCs with multidirectional differentiation potential that shifted from a chondrogenic to an osteogenic trajectory in response to mechanical tension. Mechanical tension also upregulated Dalrd3 expression and its associated tRNA m3C modification in activated SuSCs. Knockdown of Dalrd3 in SuSCs significantly impaired osteogenic differentiation, proliferation, migratory capacity, and translational activity within the bone morphogenetic protein (BMP) signaling pathway. Furthermore, Dalrd3 knockdown suppressed the translational activity of inhibitor of DNA binding 3 (Id3), a key BMP-induced mediator of osteoblastogenesis. Restoring Id3 expression in Dalrd3-deficient SuSCs rescued their osteogenic, proliferative, and migratory functions. Conclusions These findings reveal a translational regulatory mechanism in SuSCs activated by mechanical tension and underscore the pivotal role of Dalrd3 in suture remodeling and bone formation. The insights provided by this study have the potential to guide targeted therapeutic strategies for optimizing distraction osteogenesis and other treatments for craniofacial deformities. Supplementary Information The online version contains supplementary material available at 10.1186/s13287-025-04380-9.
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