Senescent Fibroblasts Drive FAP/OLN Imbalance Through mTOR Signaling to Exacerbate Inflammation and Bone Resorption in Periodontitis DOI Creative Commons

Chenghu Yin,

Liangliang Fu, Shuling Guo

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 24, 2024

Fibroblast activation protein (FAP), predominantly expressed in activated fibroblasts, plays a key role inflammatory bone diseases, but its periodontitis remains unclear. Accordingly, this study identified positive association between FAP levels and susceptibility using Mendelian randomization analysis. Human mouse tissues show elevated reduced osteolectin (OLN), an endogenous inhibitor, indicating FAP/OLN imbalance. Single-cell RNA sequencing revealed gingival fibroblasts (GFs) as the primary OLN source, with periodontitis-associated GFs showing increased reactive oxygen species, cellular senescence, mTOR pathway activation. Rapamycin treatment restored balance GFs. Recombinant pro-inflammatory cytokine secretion osteoclast differentiation macrophages, exacerbating periodontal damage, whereas inhibition macrophage inflammation, collagen degradation, resorption experimental periodontitis. Therefore, senescent drive imbalance through activation, contributing to progression. Consequently, targeting may offer promising therapeutic strategy for

Language: Английский

Tricarboxylic Acid Cycle Regulation of Metabolic Program, Redox System, and Epigenetic Remodeling for Bone Health and Disease DOI Creative Commons
Wei Lian, Re‐Wen Wu, Yu-Han Lin

et al.

Antioxidants, Journal Year: 2024, Volume and Issue: 13(4), P. 470 - 470

Published: April 17, 2024

Imbalanced osteogenic cell-mediated bone gain and osteoclastic remodeling accelerates the development of osteoporosis, which is leading risk factor disability in elderly. Harmonizing metabolic actions bone-making cells resorbing to mineralized matrix network required maintain mass homeostasis. The tricarboxylic acid (TCA) cycle mitochondria a crucial process for cellular energy production redox canonical TCA enzymes intermediates are indispensable oxidative phosphorylation adenosine triphosphate (ATP) biosynthesis differentiation osteoclast formation. Knockout mouse models identify these enzymes’ roles microarchitecture. In noncanonical processes, metabolites as co-factor or substrate involve epigenetic modification, including histone acetyltransferases, DNA demethylases, RNA m6A affect genomic stability chromatin accessibility cell metabolism formation resorption. genetic manipulation regulators intermediate supplementation compromises age, estrogen deficiency, inflammation-induced loss microstructure deterioration. This review sheds light on functions terms integrity highlights crosstalk pathways skeletal tissue treatment options delaying osteoporosis.

Language: Английский

Citations

4
Increased Alleviation of Bone Destruction in Individuals with Rheumatoid Arthritis via the Coinhibition of the METTL3 and YTHDF1 Axis by the Combination of Triptolide and Medicarpin DOI Creative Commons
Yi Jiao, Zhaoran Wang,

Wenya Diao

et al.

Engineering, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
Role and mechanisms of histone methylation in osteogenic/odontogenic differentiation of dental mesenchymal stem cells DOI Creative Commons

Meijun Hu,

Zhipeng Fan

International Journal of Oral Science, Journal Year: 2025, Volume and Issue: 17(1)

Published: March 26, 2025

Abstract Dental mesenchymal stem cells (DMSCs) are pivotal for tooth development and periodontal tissue health play an important role in engineering regenerative medicine because of their multidirectional differentiation potential self-renewal ability. The cellular microenvironment regulates the fate can be modified using various optimization techniques. These methods influence microenvironment, activate disparate signaling pathways, induce different biological effects. “Epigenetic regulation” refers to process influencing gene expression regulating cell without altering DNA sequences, such as histone methylation. Histone methylation modifications regulate transcription factors governing DMSCs into osteo-/odontogenic lineages. most sites organization were found H3K4, H3K9, H3K27. affects by maintaining a delicate balance between major trimethylation sites, generating distinct chromatin structures associated with specific downstream transcriptional states. Several crucial pathways osteogenic susceptible modulation via modifications. A deeper understanding regulatory mechanisms immune-inflammatory responses will facilitate further investigation epigenetic regulation DMSC-mediated regeneration inflammation. Here is concise overview functions at H3K27 renewal both non-inflammatory inflammatory microenvironments. This review summarizes current research on these processes context therapeutic interventions.

Language: Английский

Citations

0
Role of oxytocin in bone DOI Creative Commons
Tianming Wang,

Jianya Ye,

Yongqiang Zhang

et al.

Frontiers in Endocrinology, Journal Year: 2024, Volume and Issue: 15

Published: Sept. 3, 2024

Oxytocin (OT) is a posterior pituitary hormone that, in addition to its role regulating childbirth and lactation, also exerts direct regulatory effects on the skeleton through peripheral OT oxytocin receptor (OTR). Bone marrow mesenchymal stem cells (BMSCs), osteoblasts (OB), osteoclasts (OC), chondrocytes, adipocytes all express OTR. upregulates RUNX2, BMP2, ALP, OCN, thereby enhancing activity of BMSCs promoting their differentiation towards OB rather than adipocytes. directly regulates OPG/RANKL inhibit adipocyte generation, increase expression SOX9 COMP, enhance chondrocyte differentiation. can secrete OT, exerting influence surrounding environment autocrine paracrine mechanisms. increases OC formation NκB/MAP kinase signaling pathway, inhibits osteoclast proliferation by triggering cytoplasmic Ca2+ release nitric oxide synthesis, has dual effect OCs. Under stimulation estrogen, synthesizes amplifying biological estrogen OT. Mediated OT/OTR forms feedforward loop with OB. Apart from interacts arginine vasopressin (AVP), prostaglandins (PGE2), leptin, adiponectin regulate bone metabolism. This review summarizes recent research regulation metabolism OTR, aiming provide insights into clinical applications further research.

Language: Английский

Citations

1
Epigenetic regulation of myogenesis by vitamin C DOI

Sachiko Yamashita Takeuchi,

Chirada Dusadeemeelap,

T. Kawamoto

et al.

Journal of Cellular Physiology, Journal Year: 2024, Volume and Issue: 240(1)

Published: Oct. 24, 2024

Abstract The micronutrient vitamin C is essential for the maintenance of skeletal muscle health and homeostasis. pro‐myogenic effects have long been attributed to its role as a general antioxidant agent, well in collagen matrix synthesis carnitine biosynthesis. Here, we show that also functions an epigenetic compound, facilitating chromatin landscape transitions during myogenesis through activity enzymatic cofactor histone H3 DNA demethylation. Utilizing C2C12 myoblast cells investigate on myogenesis, observe treatment with decreases global H3K9 methylation increases 5‐hmC levels. Furthermore, enhances marker gene expression myotube formation differentiation. We identify KDM7A lysine demethylase markedly upregulated myogenesis. Accordingly, knockdown Kdm7a prevents C. Chromatin immunoprecipitation analysis showed occupies promoter region myogenic transcription factor MyoD1 where it facilitates confirm methylcytosine dioxygenases TET1 TET2 are required differentiation their loss blunts stimulation by In conclusion, our data suggest mode action plays major

Language: Английский

Citations

0
Histone demethylase PHF8 protected against chondrocyte injury and alleviated posttraumatic osteoarthritis by epigenetically enhancing WWP2 expression DOI Creative Commons
Xin Tang, Jin He,

Hao Ye

et al.

Human & Experimental Toxicology, Journal Year: 2024, Volume and Issue: 43

Published: Jan. 1, 2024

Aberrant mechanical forces were considered as an important factor for osteoarthritis (OA) pathogenesis. Plant homeodomain finger-containing protein 8 (PHF8) participated in osteogenic differentiation and inflammatory progression. However, the role of PHF8 aberrant force-related OA remains to be elucidated. In this study, a fluid shear stress (FSS) model ATDC5 cells anterior cruciate ligament transection (ACLT) animal constructed. The results revealed decrease force-induced cartilage damage vitro vivo. overexpression alleviated cell apoptosis, extracellular matrix degradation, inflammation. Chromatin immunoprecipitation (ChIP) assays demonstrated that epigenetically regulated WWP2 expression through demethylating H3K9me2 at promoter, which was influenced by FSS treatment. C-X-C chemokine receptor type 4 (CXCR4) identified potential substrate WWP2. Co-immunoprecipitation (Co-IP) ubiquitination experiments further decreased stability CXCR4 via pathway. Subsequently, rescue validated reintroduction significantly attenuated effects deletion on FSS-induced chondrocyte injury, reversed protective injury FSS-treated cells. Moreover, delivery adeno-associated virus (AAV) into articular remarkably ameliorated breakdown ACLT mice. conclusion, our findings highlighted importance PHF8/WWP2/CXCR4 signaling pathway might provide novel insight future epigenetic-based treatment posttraumatic OA.

Language: Английский

Citations

0
Senescent Fibroblasts Drive FAP/OLN Imbalance Through mTOR Signaling to Exacerbate Inflammation and Bone Resorption in Periodontitis DOI Creative Commons

Chenghu Yin,

Liangliang Fu, Shuling Guo

et al.

Advanced Science, Journal Year: 2024, Volume and Issue: unknown

Published: Dec. 24, 2024

Fibroblast activation protein (FAP), predominantly expressed in activated fibroblasts, plays a key role inflammatory bone diseases, but its periodontitis remains unclear. Accordingly, this study identified positive association between FAP levels and susceptibility using Mendelian randomization analysis. Human mouse tissues show elevated reduced osteolectin (OLN), an endogenous inhibitor, indicating FAP/OLN imbalance. Single-cell RNA sequencing revealed gingival fibroblasts (GFs) as the primary OLN source, with periodontitis-associated GFs showing increased reactive oxygen species, cellular senescence, mTOR pathway activation. Rapamycin treatment restored balance GFs. Recombinant pro-inflammatory cytokine secretion osteoclast differentiation macrophages, exacerbating periodontal damage, whereas inhibition macrophage inflammation, collagen degradation, resorption experimental periodontitis. Therefore, senescent drive imbalance through activation, contributing to progression. Consequently, targeting may offer promising therapeutic strategy for

Language: Английский

Citations

0