Biomedical Materials
·
2026
·Vol. 21
·期 1
·015022
·
IF 3.9
Liyang Chen,Heng’an Ge,Centao Liu,Jun Li,Chenglong Huang,Biao Cheng
Cartilage defects pose significant clinical challenges due to limited regenerative capacity. Dynamic matrix stiffness, mimicking the physiological mechanical microenvironment, shows promise in directing stem cell chondrogenesis, but its molecular mechanisms remain unclear. Bone marrow mesenchymal stem cells (BMSCs) were cultured on engineered hydrogels with static soft (0.033 kPa), dynamic (0.031–0.126 kPa, time-dependent stiffening), and static stiff (0.126 kPa) conditions. We performed small interfering RNA-mediated Ihh knockdown and Rcan1 overexpression, with chondrogenic differentiation assessed via COL2/SOX9 immunofluorescence. For molecular analyses, we conducted qPCR, CUT&Tag-PCR, Western blot, RNA-seq, H3K18la-targeted CUT&Tag sequencing, and transmission electron microscopy (TEM) for mitochondrial morphology assessment. Dynamic stiffness significantly enhanced chondrogenic differentiation, as evidenced by immunofluorescence detection of elevated COL2 and SOX9 expression. Ihh mRNA expression levels were upregulated by dynamic stiffness. Transcriptome profiling analysis revealed that Ihh knockdown disrupted the expression of genes involved in the glycolytic pathway, while Western blot results showed that Ihh knockdown inhibited histone H3 lysine 18 lactylation (H3K18la). CUT&Tag sequencing revealed Ihh-dependent H3K18la enrichment at regulatory regions of mitochondria-associated genes, notably Rcan1. Ihh deficiency promoted mitochondrial fission, as evidenced by increased Drp1 and Fis1 mRNA expression levels and direct observation of enhanced mitochondrial fission via TEM. Crucially, Rcan1 overexpression rescued mitochondrial fusion, downregulated fission markers, and reinstated chondrogenic marker expression. Consistently, the LDHA inhibitor FX11 reduced lactate levels, diminished H3K18la, and downregulated Rcan1, confirming the metabolic dependence of this axis. RNA-seq analysis further established that Rcan1 overexpression reprogrammed signaling pathways critical for cell differentiation, including ECM-receptor interaction. Dynamic stiffness promotes BMSC chondrogenesis via the Ihh-H3K18la-Rcan1 axis, linking mechanical cues to epigenetic regulation of mitochondrial remodeling and providing a novel target for cartilage repair.
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DOI
高影响因子
JOURNAL OF MATERIALS SCIENCE
·
2016
·Vol. 52
·期 8
·4713-4726
·
IF 2.302
Zhang Xiaoyan,Hu Xiaoling,Guan Ping,Zhang Nan,Li Ji,Du Chunbao
In this work, super-paramagnetic interface molecularly imprinted microspheres (MIMIMs) were prepared using an immunostimulating hexapeptide as template via photo-initiated Pickering emulsion polymerization by the self-assembly of the template-immobilized silica nanoparticles at the oil–water interface under room temperature. The whole experiment process was tracked and analyzed by various characterization methods. Results manifest that the obtained MIMIMs showed excellent recognition property and rapid-efficiency separation for template peptide due to their accessible imprinted sites and desired magnetic susceptibility. Moreover, MIMIMs were used in competitive rebinding and reusability tests, which demonstrated their potential application in the enrichment of IHH and sustainable performance in resource-saving.
研究领域:
材料科学
·
纳米技术
·
生物医学工程
·
分析化学
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产品关联
DOI
高影响因子
JOURNAL OF CELLULAR AND MOLECULAR MEDICINE
·
2024
·Vol. 28
·期 23
·e70271
·
IF 4.3
Zongrui Yang,Yuanyuan Feng,Mingcai Zhang,Yongming Liu,Yizhe Xiong,Xiang Wang,Ying Shi,Bo Chen,Zhengming Wang,Haiya Ge,Hongsheng Zhan,Zhibi Shen,Guoqing Du
HBP-A is the main active component of a traditional Chinese medicine Huaizhen Yanggan Capsule, for the remarkable treatment of knee osteoarthritis (KOA). This study aimed to elucidate the ameliorative effect of HBP-A on meniscus hypertrophy and mineralisation in KOA and the molecular mechanism of its action. An Hartley guinea pig model of KOA that underwent anterior cruciate ligament transection (ACLT) and a model of rat primary meniscus fibrochondrocytes (PMFs) were used to investigate the ameliorative effect of HBP-A on meniscal hypertrophy and calcification and its signal transduction mechanism of action. The results show that Guinea pig's meniscus width, as well as the area of meniscus calcification and meniscus and articular cartilage injury score, were significantly reduced in the HBP-A intervention group compared to the ACLT group. The expression levels of mtrix metalloproteinase 13 (MMP13), runt-related transcription factor 2 (Runx2), Indian hedgehog (Ihh), alkaline phosphatase (ALP), and ankylosis homologue (ANKH) at the protein and gene level significantly decreased in the HBP-A intervention group compared to the ACLT group. In vitro study, apoptosis, hypertrophy, and calcification of rat PMFs after 10% stretch force were significantly improved with HBP-A intervention. Western blot and RT-qPCR showed that hypertrophy, calcification, and p38 MAPK signalling pathway-related markers of PMFs were incredibly depressed in the HBP-A intervention group compared to the 10% stretch force group. In conclusion, HBP-A can slow down meniscus hypertrophy and mineralisation induced by abnormal mechanical loading, and its mechanism of action may be through the p38-MAPK signalling pathway.
研究领域:
药理学
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骨科
·
分子生物学
·
传统中药
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产品关联
DOI
PubMed
高影响因子
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