Cartilage Homeostasis under Physioxia

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(17), P. 9398 - 9398

Published: Aug. 29, 2024

Articular cartilage receives nutrients and oxygen from the synovial fluid to maintain homeostasis. However, compared tissues with abundant blood flow, articular is exposed a hypoxic environment (i.e., physioxia) has an enhanced stress response. Hypoxia-inducible factors (HIFs) play pivotal role in this physioxic environment. In normoxic conditions, HIFs are downregulated, whereas they upregulated. The HIF-α family comprises three members: HIF-1α, HIF-2α, HIF-3α. Each member distinct function cartilage. osteoarthritis, which primarily caused by degeneration of cartilage, HIF-1α upregulated chondrocytes believed protect acting anabolically on it. Conversely, contrast HIF-2α exerts catabolic influence It may therefore be possible develop new treatment for OA controlling expression drugs or altering joints.

Language: Английский

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The role of circadian rhythm regulator PERs in oxidative stress, immunity, and cancer development

Cell Communication and Signaling, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 16, 2025

The complex interaction between circadian rhythms and physiological functions is essential for maintaining human health. At the heart of this lies PERIOD proteins (PERs), pivotal to clock, influencing timing behavioral processes impacting oxidative stress, immune functionality, tumorigenesis. PER1 orchestrates cooperation enzyme GPX1, modulating mitochondrial dynamics in sync with daily thus regulating mechanisms managing energy substrates. PERs innate cells modulate temporal patterns NF-κB TNF-α activities, as well response LPS-induced toxic shock, initiating inflammatory responses that escalate into chronic conditions. Crucially, cancer cell behaviors including proliferation, apoptosis, migration by levels cycle stimulating expression oncogenes c-Myc MDM2. PER2/3, antagonists stem biology, play important roles differentiating their stemness. Importantly, Pers serve a significant factor early diagnosis prognosis. This review delves link rhythm regulator PERs, disruptions rhythm, oncogenesis. We examine evidence highlights how dysfunctions activities initiate development, aid tumor growth, modify metabolism through pathways involved stress system. Comprehending these connections opens new development rhythm-based therapeutic strategies, aims boosting enhancing treatments.

Language: Английский

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Rethinking Osteoarthritis Management: Synergistic Effects of Chronoexercise, Circadian Rhythm, and Chondroprotective Agents

Biomedicines, Journal Year: 2025, Volume and Issue: 13(3), P. 598 - 598

Published: March 1, 2025

Osteoarthritis (OA) is a chronic and debilitating joint disease characterized by progressive cartilage degeneration for which no definitive cure exists. Conventional management approaches often rely on fragmented poorly coordinated pharmacological non-pharmacological interventions that are inconsistently applied throughout the course. Persistent controversies regarding clinical efficacy of chondroprotective agents, frequently highlighted pharmacovigilance agencies, underscore need structured evidence-based approach. Emerging evidence suggests synchronizing pharmacotherapy exercise regimens with circadian biology may optimize therapeutic outcomes addressing early pathological processes, including low-grade inflammation, oxidative stress, matrix degradation. Recognizing influence chondrocyte clock these this study proposes ‘prototype’ novel framework leverages rhythm-aligned administration traditional agents along tailored, accessible protocols to mitigate breakdown support function. In addition, model-based emphasizes interdependence between chronobiology time-of-day-dependent responses exercise, where strategically timed activity enhances nutrient waste exchange, mitigates mitochondrial dysfunction, supports cellular metabolism, promotes tissue maintenance, whereas nighttime rest rehydration repair. This time-sensitive, comprehensive approach aims slow OA progression, reduce structural damage, delay invasive procedures, particularly in weight-bearing joints such as knee hip. However, significant challenges remain, inter-individual variability rhythms, lack reliable biomarkers pharmacotherapeutic monitoring, limited supporting chronoexercise protocols. Future large-scale, longitudinal trials critical evaluate scalability rational integrative strategy, paving way new era management.

Language: Английский

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Bamboo Leaf Flavonoids from Phyllostachys glauca McClure Suppress the Progression of Alzheimer’s Disease Induced by Circadian Rhythm Disruption Through Regulating Hif3α/Rab7/TNFα/IL1β Pathway

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3169 - 3169

Published: March 29, 2025

Circadian rhythm disruption is a modifiable risk factor for Alzheimer’s disease (AD) progression, marked by neuroinflammation, oxidative stress, and amyloid-β (Aβ) accumulation. Hypoxia-inducible 3α (Hif3α) has emerged as key regulator of inflammatory pathways. To evaluate the impacts circadian on AD progression investigate therapeutic potential bamboo leaf flavonoids (BLFs), C57BL/6N mice (normal mice) APP/PS1 transgenic (AD were exposed to via randomized light exposure in vivo model. Then, BLFs administered assess effects organ damage. Next, Nissl body staining Aβ protein immunohistochemistry performed brain pathology. Through transcriptome sequencing, factors related pathway screened out. In vitro, molecular mechanisms explored PC12 cells treated with Aβ42 Hif3α siRNA fragments. Results demonstrated that increased stress early liver kidney damage degrees, greater severity mice. partially reversed reduced deposition. Transcriptome analysis revealed upregulation circadian-disrupted mice, linked inflammation stress. knockdown normalized expression, which could be regulated suppressed progression. conclusion, exacerbated regulating Hif3α/Rab7/TNFα/IL1β pathway. offered neuroprotection roles mitigating damage, highlighting promising target therapy biomarker development.

Language: Английский

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Future perspectives: advances in bone/cartilage organoid technology and clinical potential.

PubMed, Journal Year: 2024, Volume and Issue: 5(4), P. 425 - 443

Published: Jan. 1, 2024

Bone and cartilage tissues are essential for movement structure, yet diseases like osteoarthritis affect millions. Traditional therapies have limitations, necessitating innovative approaches. Organoid technology, leveraging stem cells' regenerative potential, offers a novel platform disease modelling therapy. This review focuses on advancements in bone/cartilage organoid highlighting the role of cells, biomaterials, external factors development. We discuss implications these organoids medicine, research, personalised treatment strategies, presenting as promising avenue enhancing repair bone regeneration. Bone/cartilage will play greater future, promote progress biological tissue engineering.

Language: Английский

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Angiogenesis unveiled: Insights into its role and mechanisms in cartilage injury

Experimental Gerontology, Journal Year: 2024, Volume and Issue: 195, P. 112537 - 112537

Published: Aug. 6, 2024

Osteoarthritis (OA) commonly results in compromised mobility and disability, thereby imposing a significant burden on healthcare systems. Cartilage injury is prevalent pathological manifestation OA constitutes central focus for the development of treatment strategies. Despite considerable number studies aimed at delaying this degenerative process, their outcomes remain unvalidated preclinical settings. Recently, therapeutic strategies focused angiogenesis have attracted growing interest from researchers. Thus, we conducted comprehensive literature review to elucidate current progress research pinpoint gaps domain. Additionally, it provides theoretical guidance future endeavors

Language: Английский

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