The multifunctional regulatory post-proline protease dipeptidyl peptidase 9 and its inhibitors: new opportunities for therapeutics DOI Creative Commons

Jennifer M. K. Nguyen,

Samuel Zolg,

Ruth Geiss‐Friedlander

et al.

Cellular and Molecular Life Sciences, Journal Year: 2025, Volume and Issue: 82(1)

Published: April 28, 2025

Abstract Dipeptidyl Peptidase 9 (DPP9) is a prolyl amino dipeptidylpeptidase that can cut post-proline peptide bond at the penultimate position N-terminus. By removing N-terminal prolines, this intracellular peptidase acts as an upstream regulator of N-degron pathway. DPP9 has crucial roles in inflammatory regulation, DNA repair, cellular homeostasis, and proliferation, while its deregulation linked to cancer immunological disorders. Currently, there no fully selective chemical inhibitor knockout transgenic mouse model conditional. Mice humans which catalytic activity absent die neonatally. inhibition for manipulating vivo potential uses rapid progress towards selectivity, with 170x selectivity achieved. This review discusses biology diseases applications compounds inhibit related proteases.

Language: Английский

Regulation and functional importance of human periodontal ligament mesenchymal stromal cells with various rates of CD146+ cells DOI Creative Commons
Oliwia Miłek, Katharina Schwarz,

Alma Tihana Miletić

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: March 7, 2025

Introduction Mesenchymal stromal cells (MSCs) with high expression of CD146 have superior properties for tissue regeneration. However, variability in the rate CD146+ among donors is observed. In this study, possible reasons behind human periodontal ligament MSCs (hPDL-MSCs) were explored. Methods hPDL-MSCs isolated from 22 different donors, and rates analyzed by flow cytometry. Furthermore, populations various magnetic separation. The dependency cell proliferation, viability, cycle, osteogenic differentiation on was investigated. Besides, effects factors, like density, confluence, inflammatory environment analyzed. Results exhibited between percentage ranging 3% to 67%. Higher associated higher presumably due S-phase, potential. Prolonged confluence seeding density led decline cells. surface stimulated treatment interleukin-1β tumor necrosis factor-α, inhibited interferon-γ. Conclusion These results suggest that are a promising subpopulation enhancing effectiveness MSC-based regenerative therapies, however affected which must be considered propagation their potential application vivo .

Language: Английский

Citations

1

Editorial: Perivascular niche and stem cell signaling in tooth DOI Creative Commons
Takehito Ouchi, Emi Shimizu, Bo Li

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 31, 2025

Perivascular niche is the micro space that serves as a stem cell reservoir and an essential part of maintaining physiological conditions influencing pathological dental tissues (Shi et al., 2003). Senescence one most important elements in regulating ability (López-Otín 2023). Most recently, Li al. presented first spatially resolved transcriptomic landscape murine jawbone including tissues, uncovered DNA methylation crucial mechanism underlying transforming growth factor beta 1 (TGF-β1)-induced periodontal ligament (PDLSC) senescence (Li 2024). Ju reported ectonucleotide pyrophosphatase/phosphodiesterase (ENPP) for TGF-β1-induced PDLSC differentiation (Ju al.). ENPP modulates mineralization efficacy driven by adenosine triphosphate released from pulp cells response to intrapulpal pressure (Techatharatip 2018). In observing behavior, differentiation, maturity, spatiotemporal understanding between blood vessels, mouse incisor good model tracing cellular genetic changes. pulp, there are fundamental cell-to-cell communications orchestrate tooth formation, angiogenic-odontogenic coupling, distinct compared angiogenic-osteogenic coupling bones (Matsubara 2022).Tooth formation complex process controlled information environmental factors (Murashima-Suginami 2021). Because root dentin it valuable clarify precise control mechanisms more specifically, root. Due different crown, several unique must be involved dentin. Identifying these may help understand adult regeneration. Cui harvested labial lingual sides incisors conducted microarray analysis. Gene ontology (GO) analysis differentially expressed genes indicated critical role extracellular matrix discrepancy which hemicentin-1 (Hmcn1) was selected target gene. addition, single-cell RNA sequencing showed expression pattern Hmcn1 at developmental stages molars (Cui The HMCN1 detected immunohistochemical staining well. This group also investigated functions human cells, proliferation, migration. Uncovering patterns complicated but precisely differential gene will strengthen tissue area-specific treatment future.Both rodent have multiple roots formed through similar sequences. It considered its surrounding structures PDL alveolar bone eruption (Ono 2016). Tooth eruption, development regeneration, involves anabolism catabolism. Periodontium, surrounds teeth, derived follicle (DFSCs). During DFSCs inhibit osteoclast releasing vesicles containing Annexin A1 (ANXA1) mediated pathway, thereby preventing premature eruption.Elucidation this extremely abnormal diseases regeneration (Sun al.).Teeth able regenerate due inherent autonomous their constituent cells. However, once huge deformation occurs, difficult reproduce integrated nature tissue. situation calls regenerative therapies using bioengineering tools maximize potential (Yang 2019).Zheng N-acetylcysteine (NAC) stable, safe, highly bioavailable antioxidant shows promising prospects engineering attenuate oxidative stress enhance osteogenic immune regulatory function systematically introduced NAC, analyzed advancements NAC-related research involving mesenchymal (MSCs), precursor innate animal models, discussed function, placed particular emphasis on innovative applications NAC-modified biomaterials (Zheng al.).Perivascular MSCs express NOTCH3 they very composed identical subpopulations. addition perivascular MSCs, endothelial Schwann fibroblasts, etc. construct niches (Pagella Understanding homeostasis maintenance intra signals promote medicine. Dental participate development, shed light designing next-generation strategies achieve eventual goal de novo (Hu 2022). regard, further studies vascular involvement technology support acceleration medicine.TO, ES, BL wrote editorial invited authors collection. All contributed article approved submitted version.

Language: Английский

Citations

0

Dasatinib and Quercetin Mitigate Age‐Related Alveolar Bone Inflammaging and Neutrophil Infiltration DOI Open Access

Jie Tang,

Jingya Li,

Zeyu Hou

et al.

Oral Diseases, Journal Year: 2025, Volume and Issue: unknown

Published: March 6, 2025

Age-related alveolar bone resorption poses a major dental health challenge, yet its mechanisms and treatments are poorly understood. This study investigates the impact of dasatinib quercetin (D + Q) treatment on senescent cells (SnCs), senescence-associated secretory phenotype (SASP), neutrophil infiltration in aged bone, aiming to develop new strategies for combating age-related resorption. C57BL/6 mice (2 18 months) were used examine resorption, inflammaging, infiltration. Aged received D Q assess therapeutic effects. Key measurements included cementoenamel junction crest (CEJ-ABC) distance, periodontal ligament (PDL) thickness, osteometabolism markers, SnCs accumulation, SASP expression, showed increased CEJ-ABC atrophied ligament, unbalanced osteometabolism, along with elevated SnCs, SASP, neutrophils compared young controls. improved these conditions by reducing enhancing health, boosting metabolism. It also lowered expression markers. effectively mitigates aging clearing lowering levels, aggregation, presenting novel approach

Language: Английский

Citations

0

Histological and immunohistochemical analysis of human periapical lesions: a study of TGF-β1 and CD68 markers DOI Creative Commons
Nermeen AbuBakr, Geraldine Ahmed, Amany Hany Mohamed Kamel

et al.

BMC Oral Health, Journal Year: 2025, Volume and Issue: 25(1)

Published: April 11, 2025

Language: Английский

Citations

0

Differentiated muscle cells of salamander Pleurodeles waltl re-enter the cell cycle DOI

Hao Cai,

Yao Hua,

Shihao Wang

et al.

Histochemistry and Cell Biology, Journal Year: 2025, Volume and Issue: 163(1)

Published: April 17, 2025

Language: Английский

Citations

0

The multifunctional regulatory post-proline protease dipeptidyl peptidase 9 and its inhibitors: new opportunities for therapeutics DOI Creative Commons

Jennifer M. K. Nguyen,

Samuel Zolg,

Ruth Geiss‐Friedlander

et al.

Cellular and Molecular Life Sciences, Journal Year: 2025, Volume and Issue: 82(1)

Published: April 28, 2025

Abstract Dipeptidyl Peptidase 9 (DPP9) is a prolyl amino dipeptidylpeptidase that can cut post-proline peptide bond at the penultimate position N-terminus. By removing N-terminal prolines, this intracellular peptidase acts as an upstream regulator of N-degron pathway. DPP9 has crucial roles in inflammatory regulation, DNA repair, cellular homeostasis, and proliferation, while its deregulation linked to cancer immunological disorders. Currently, there no fully selective chemical inhibitor knockout transgenic mouse model conditional. Mice humans which catalytic activity absent die neonatally. inhibition for manipulating vivo potential uses rapid progress towards selectivity, with 170x selectivity achieved. This review discusses biology diseases applications compounds inhibit related proteases.

Language: Английский

Citations

0