Senescent cells impair fracture repair through elevating ubiquitin-proteasome system activity in aged mice DOI Open Access
Jun Zhang,

Jiongnan Xu,

Jiatong Liu

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2023, Номер unknown

Опубликована: Ноя. 4, 2023

Abstract Senescent cells accumulate in multiple tissues with aging. Depletion of senescent benefits the aging related disease, such as bone fracture. However, molecular mechanisms by which regulate their neighboring are still not well-known. We reported that proteasome inhibitor enhanced fracture repair aged mice. major source chronic inflammatory cytokines, turn induced protein ubiquitination. PDGFRβ was one highly ubiquitinated proteins mesenchymal progenitors (MPCs) and TGFβ most increased SASP. In current study, we found ubiquitination proteasomal degradation through its E3 ligases. neutralizing antibody blocked inhibited callus derived MPC growth Ub-PDGFRβ cells, could be further prevented inhibitor. These findings suggested impaired mice elevating PDGFRβ. The discovery TGFβ-PDGFRβ pathway triggered opens avenues for optimizing treatment strategies disease combination ligand

Язык: Английский

Targeting chronic inflammation as a potential adjuvant therapy for osteoporosis DOI
Gregory Livshits, Alexander Kalinkovich

Life Sciences, Год журнала: 2022, Номер 306, С. 120847 - 120847

Опубликована: Июль 28, 2022

Язык: Английский

Процитировано

37
Fisetin, a Natural Polyphenol, Ameliorates Endometriosis Modulating Mast Cells Derived NLRP-3 Inflammasome Pathway and Oxidative Stress DOI Open Access

Alessia Arangia,

Ylenia Marino,

Roberta Fusco

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(6), С. 5076 - 5076

Опубликована: Март 7, 2023

A chronic, painful, and inflammatory condition known as endometriosis is defined by the extra-uterine development of endometrial tissue. The aim this study was to evaluate beneficial effects fisetin, a naturally occurring polyphenol that frequently present in variety fruits vegetables. Uterine fragments were injected intraperitoneally cause endometriosis, fisetin given orally every day. At 14 days treatment, laparotomy performed, implants peritoneal fluids collected for histological, biochemical, molecular analyses. Rats subjected presented important macroscopic microscopic changes, increased mast cell (MC) infiltration, fibrosis. Fisetin treatment reduced endometriotic implant area, diameter, volumes, well histological alterations, neutrophil cytokines release, number MCs together with expression chymase tryptase, diminished α smooth muscle actin (α-sma) transforming growth factor beta (TGF β) expressions. In addition, able reduce markers oxidative stress nitrotyrosine Poly ADP ribose expressions increase apoptosis lesions. conclusion, could represent new therapeutic strategy control perhaps targeting MC-derived NOD-like receptor family pyrin domain containing 3 (NLRP3) inflammasome pathway stress.

Язык: Английский

Процитировано

19
Adipose Mesenchymal Stem Cell-Derived Exosomes Promote the Regeneration of Corneal Endothelium Through Ameliorating Senescence DOI Creative Commons

Yun‐Kyoung Ryu,

Jin Sun Hwang,

Kyung Bo Noh

и другие.

Investigative Ophthalmology & Visual Science, Год журнала: 2023, Номер 64(13), С. 29 - 29

Опубликована: Окт. 18, 2023

Human corneal endothelial cells (hCECs) have been considered unable to regenerate in vivo, resulting decompensation after significant loss of hCECs. adipose-derived mesenchymal stem cell (ASC)-derived exosomes can tissues and organs. In this study, we investigated whether ASC-derived could protect CECs.We performed viability cell-cycle analyses evaluate the effect on regeneration capacity cultured Transforming growth factor-β (TGF-β) hydrogen peroxide (H2O2) were used induce biological stress CECs. The CECs was vivo. introduced into rat using electroporation, corneas injured cryoinjury. Next-generation sequencing analysis compare differentially expressed microRNAs (miRNAs) between hCEC-derived exosomes.ASC-derived induced CEC proliferation suppressed TGF-β- or H2O2-induced oxidative senescence. hCECs against endothelial-mesenchymal transition mitophagy. an vivo promoted wound healing protected endothelium cryoinjury-induced damage. revealed miRNAs for exosomes. They are involved lysine degradation, adherens junction, TGF-β signaling pathway, p53 Hippo forkhead box O (FoxO) regulation actin cytoskeleton, RNA degradation based Kyoto Encyclopedia Genes Genomes (KEGG) pathway analysis.ASC-derived by inducing a shift cycle suppressing senescence autophagy.

Язык: Английский

Процитировано

19
Balancing the Scales: The Dual Role of Interleukins in Bone Metastatic Microenvironments DOI Open Access
Ahmad Dawalibi,

Amal Alosaimi,

Khalid S. Mohammad

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(15), С. 8163 - 8163

Опубликована: Июль 26, 2024

Bone metastases, a common and debilitating consequence of advanced cancers, involve complex interplay between malignant cells the bone microenvironment. Central to this interaction are interleukins (ILs), group cytokines with critical roles in immune modulation inflammation. This review explores dualistic nature pro-inflammatory anti-inflammatory emphasizing their molecular mechanisms, pathological impacts, therapeutic potential. Pro-inflammatory interleukins, such as IL-1, IL-6, IL-8, have been identified key drivers promoting osteoclastogenesis, tumor proliferation, angiogenesis. These create favorable environment for cancer cell survival degradation, contributing progression metastatic lesions. Conversely, including IL-4, IL-10, IL-13, exhibit protective by modulating responses inhibiting osteoclast activity. Understanding these opposing effects is crucial developing targeted therapies aimed at disrupting processes metastases. Key signaling pathways, NF-κB, JAK/STAT, MAPK, mediate actions influencing survival, recruitment, remodeling. Targeting pathways presents promising avenues. Current treatment strategies, use denosumab, tocilizumab, emerging agents like bimekizumab ANV419, highlight potential interleukin-targeted mitigating However, challenges resistance, side effects, long-term efficacy remain significant hurdles. also addresses diagnostic prognostic biomarkers, offering insights into patient stratification personalized approaches. Interleukins multifaceted that depend on context, environment, types, cellular interactions. Despite substantial progress, gaps research persist, particularly regarding precise mechanisms which influence niche broader clinical implications. While not exhaustive, overview underscores metastases highlights need continued fully elucidate interactions Addressing will be essential advancing our understanding patients.

Язык: Английский

Процитировано

4
Mechanistic insights into bone remodelling dysregulation by human viral pathogens DOI
Camila Carla da Silva Caetano, Tamiris Azamor,

Nikki M. Meyer

и другие.

Nature Microbiology, Год журнала: 2024, Номер 9(2), С. 322 - 335

Опубликована: Фев. 5, 2024

Язык: Английский

Процитировано

3
Citrate: a key signalling molecule and therapeutic target for bone remodeling disorder DOI Creative Commons
Qichang Liu,

Yuchuan Xue,

Jiajie Guo

и другие.

Frontiers in Endocrinology, Год журнала: 2025, Номер 15

Опубликована: Янв. 16, 2025

Bone remodeling is a continuous cyclic process that maintains and regulates bone structure strength. The disturbance of leads to series metabolic diseases. Recent studies have shown citrate, an intermediate metabolite the tricarboxylic acid (TCA) cycle, plays important role in remodeling. But exact mechanism still unclear. In this study, we focused on systemic regulatory citrate remodeling, found involved multiple ways. participation oxidative phosphorylation (OXPHOS) facilitates generation ATP, thereby providing substantial energy for formation resorption. Osteoclast-mediated resorption releases from mineral salts, which subsequently released as source activate osteogenic differentiation stem cells. Finally, differentiated osteoblasts secrete into matrix participate salts formation. As substrate histone acetylation, expression genes related reabsorption. Citrate also key metabolism synthesis glucose, fatty acids amino acids, are three major nutrients organism. can be used biomarker monitor mass transformation diagnosis therapeutic evaluation disorders. imbalance due transporter could result supression osteoblast/OC function through contributing disorders Therefore, designing drugs targeting citrate-related proteins regulate content provides new direction drug treatment diseases

Язык: Английский

Процитировано

0
Exercise alleviates osteoporosis by regulating the secretion of the Senescent Associated Secretory Phenotype DOI

Weng Kaihong,

Yuting He, Weng Xi-quan

и другие.

Bone, Год журнала: 2025, Номер unknown, С. 117485 - 117485

Опубликована: Апрель 1, 2025

Язык: Английский

Процитировано

0
Research on the role and mechanism of the PI3K/Akt/mTOR signalling pathway in osteoporosis DOI Creative Commons
Chia‐Yang Liu, Jianqiang Zhang, Ziyu Ye

и другие.

Frontiers in Endocrinology, Год журнала: 2025, Номер 16

Опубликована: Май 12, 2025

Osteoporosis is a systemic metabolic bone disease characterised mainly by reduced mass, microstructure degradation, and loss of mechanical properties. As the world population ages, more than 200 million people worldwide suffer from pain caused osteoporosis every year, which severely affects their quality life. Moreover, prevalence continues to increase. The pathogenesis highly complex closely related apoptosis, autophagy, oxidative stress, inflammatory response, ferroptosis. PI3K/Akt/mTOR signalling pathway one most crucial intracellular signal transduction pathways. This not only involved in metabolism remodelling but also proliferation differentiation osteoblasts, osteoclasts, marrow mesenchymal stem cells. Abnormal activation or inhibition can disrupt balance between osteoblast-mediated formation osteoclast-mediated resorption, ultimately leading development osteoporosis. review summarises molecular mechanisms mediates five pathological mechanisms, namely, ferroptosis, regulation osteoporosis, aiming provide theoretical basis for novel effective therapeutic drugs intervention measures prevention treatment.

Язык: Английский

Процитировано

0
Blockade of IL-1 family cytokines in the treatment of rheumatoid arthritis DOI Creative Commons
Kexin Wang,

Haoge Luo,

Liping Liu

и другие.

Frontiers in Pharmacology, Год журнала: 2025, Номер 16

Опубликована: Май 30, 2025

Rheumatoid arthritis (RA), a chronic autoimmune disorder, imposes substantial global health burden through elevated disability rates, systemic complications, and socioeconomic consequences. Chronic synovitis progressive joint destruction characterize this disease, driven by dysregulated innate adaptive immune responses that amplify synovial inflammation, osteoclastogenesis, irreversible tissue damage. Aberrant activation of interleukin (IL) -1 family cytokines critically contributes to RA pathogenesis. These mediate dual mechanisms: pro-inflammatory agonists like IL-1β, IL-18, IL-36 accelerate disease progression, whereas insufficient levels anti-inflammatory antagonists such as IL-1Ra IL-37 disrupt the balance required suppress pathogenic cascades. Clinical trials evaluating IL-1-targeting biologics—including anakinra canakinumab—have demonstrated robust early efficacy. However, late-stage interventions exhibit diminished therapeutic returns, largely due damage compensatory redundant cytokine networks. findings emphasize need for precise patient stratification. Single-pathway IL-1 inhibition faces inherent limitations, driving development multi-target strategies counteract redundancy reduce resistance. This review systematically analyzes mechanistic roles in RA, evaluates clinical outcomes safety profiles IL-1-targeted therapies, proposes innovative advance treatment.

Язык: Английский

Процитировано

0
MicroRNA-mediated epigenetic regulation of inflammasomes in inflammatory responses and immunopathologies DOI
Young‐Su Yi

Seminars in Cell and Developmental Biology, Год журнала: 2022, Номер 154, С. 227 - 238

Опубликована: Ноя. 25, 2022

Язык: Английский

Процитировано

14