Periodontitis is a chronic inflammatory disease characterized by plaque accumulation, resulting in immune microenvironment disorders and resorption of alveolar bone. To promote bone healing under inflammatory environments, a functional biomaterial based on disease pathophysiology is designed. A novel fatty acid C10-modified polypeptide, C-KR8, is discovered to have excellent abilities in modulating macrophage repolarization and promoting bone regeneration in periodontitis. To build a multifunctional material localized drug delivery system, C-KR8@ZIF-8 (C-KR8-loaded zeolitic imidazolate framework-8) nanoparticles are constructed to sustainedly release the C-KR8 peptide and Zn elements. By synergistic effects of providing a dynamic immuno-modulatory environment and promoting osteogenesis under pathological conditions, the obtained pH-responsive nanoparticles display excellent bone regeneration capability. Furthermore, coimmunoprecipitation/liquid chromatography-tandem mass spectrometry analysis and proteomics analysis revealed that the C-KR8 peptide directly interacts with the high-temperature requirement protein A1 (Htra1), and C-KR8@ZIF-8 nanoparticles promote the osteogenic differentiation of bone mesenchymal stem cells by activating the focal adhesion kinase (FAK)/phosphatidylinositide 3-kinase (PI3K)/AKT pathway and enhancing the nuclear localization of Yes-associated protein (YAP). Taken together, this study demonstrates C-KR8 peptide regulate osteoimmunology and bone regeneration by Htra1/FAK/YAP pathway and that ZIF-8-based peptide loading platform is a promising strategy for periodontitis.
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http://dx.doi.org/10.34133/bmr.0057 | DOI Listing |
Patient-specific induced pluripotent stem cells (iPSCs)-based modeling potentially recapitulates the pathology and mechanisms more faithfully than cell line models and general animal models. Utilizing iPSC-derived cells for personalized bone formation research offers a powerful tool to better understand the role of individual differences in bone health and disease and provide more precise information for personalized bone regeneration therapies. Here we generated iPSC-derived mesenchymal progenitor cells (iMPCs), endothelial cells (iECs), and macrophages (iMØ), from different donors.
View Article and Find Full Text PDFJ Oral Biosci
December 2024
Division of Anatomical and Cellular Pathology, Department of Pathology, Iwate Medical University, 1-1-1 Idaidori, Yahaba-cho, Shiwa-gun, Iwate, 028-3694, Japan. Electronic address:
Objective: This study aimed to evaluate the role of the chromodomain helicase DNA-binding protein 3 (CHD3) in tooth morphogenesis in Chd3 knockout mice.
Methods: Chd3 knockout mice were generated using the CRISPR-Cas9 method. Mandibular first molars were extracted from the mice and their littermates and morphometrically analyzed.
Cell Signal
December 2024
State Key Laboratory of Oral & Maxillofacial Reconstruction and Regeneration, Key Laboratory of Oral Biomedicine Ministry of Education, Hubei Key Laboratory of Stomatology, School & Hospital of Stomatology, Wuhan University, Wuhan, China; Department of Periodontology, School & Hospital of Stomatology, Wuhan University, Wuhan, China. Electronic address:
Periodontitis (PD) is twice as prevalent in diabetics compared to nondiabetics, and diabetes-associated PD is characterized by increased inflammation and aggravated tissue damage. Pyroptosis has recently been implicated in diabetes-associated PD; however, the underlying mechanisms remain largely unknown, resulting in a lack of effective treatments. In this study, we investigated the role of methyltransferase-like 3 (METTL3) in macrophage pyroptosis and found that it inhibits the osteogenic differentiation of osteoblasts via pyroptotic macrophages in a diabetes-associated periodontitis mouse model.
View Article and Find Full Text PDFJ Mol Med (Berl)
December 2024
Department of Oral & Maxillofacial Surgery, Xiangya Stomatological Hospital & Xiangya School of Stomatology, Central South University, Central South University, Changsha, 410000, China.
Adipose-derived stem cells (ADSCs) have become one of the best seed cells widely studied and concerned in tissue engineering because of their rich sources and excellent multi-directional differentiation ability, which are expected to play a practical application role in tissue defect, osteoporosis, plastic surgery, and other fields. However, the differentiation direction of ADSCs is regulated by complex factors. Long non-coding RNAs (lncRNAs) are RNA molecules longer than 500 nucleotides that do not encode proteins and can act as signaling RNAs in response to intracellular and extracellular stimuli.
View Article and Find Full Text PDFJ Drug Target
December 2024
Department of Pharmaceutics, School of Pharmacy & Technology Management, SVKM'S Narsee Monjee Institute of Management Studies, Shirpur-425405, Maharashtra, India.
The occurrence of oral bone tissue degeneration and bone defects by osteoporosis, tooth extraction, obesity, trauma, periodontitis, and congenital defects are major challenges for clinicians. Traditional bone regeneration methods, although exhibiting efficacy to a certain degree, often come with limitations such as donor site morbidity, limitation of special shape, inflammation, and resorption of the implanted bone. The treatment oriented with biomimetic bone materials has achieved significant attention recently.
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