Articular cartilage degeneration and aberrant osteocyte perilacunar/canalicular remodeling in subchondral bone of patients with developmental dysplasia of the hip

BMC Musculoskeletal Disorders, Journal Year: 2025, Volume and Issue: 26(1)

Published: Feb. 18, 2025

Developmental dysplasia of the hip (DDH) is a congenital musculoskeletal disease that impairs joint and exacerbates osteoarthritis. This study aims to investigate alterations osteocytic characteristics including apoptosis, lacuna-canalicular network, perilacunar/canalicular remodeling (PLR) activity in subchondral bone from DDH patients, potential relationship these between cartilage degeneration progression. The femoral head specimens were acquired 16 patients with fractures who received total arthroplasty operation, 24 primary OA 25 DDH. scanned by micro-computed tomography volume interest was used for micro-finite element analysis. Histological immunohistochemical staining observe chondrocytes osteocytes bone. Terminal deoxynucleotidyl transferase dUTP nick end labeling apoptotic Ploton silver visualize lacunocanalicular network picrosirius red collagen fiber orientation group showed highest apoptosis rate increased PLR among three groups. micro–finite-element analysis revealed had deteriorative microstructural biomechanical properties histological analyses most severe. Linear regression significant correlation Our findings indicate abnormal osteocyte might contribute deterioration structure, which accelerates Targeting could offer promising therapeutic strategy

Language: Английский

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Unveiling the ageing-related genes in diagnosing osteoarthritis with metabolic syndrome by integrated bioinformatics analysis and machine learning

Artificial Cells Nanomedicine and Biotechnology, Journal Year: 2025, Volume and Issue: 53(1), P. 57 - 68

Published: March 1, 2025

Ageing significantly contributes to osteoarthritis (OA) and metabolic syndrome (MetS) pathogenesis, yet the underlying mechanisms remain unknown. This study aimed identify ageing-related biomarkers in OA patients with MetS. MetS datasets genes (ARGs) were retrieved from public databases. The limma package was used differentially expressed (DEGs), weighted gene coexpression network analysis (WGCNA) screened modules, machine learning algorithms, such as random forest (RF), support vector (SVM), generalised linear model (GLM), extreme gradient boosting (XGB), employed. nomogram receiver operating characteristic (ROC) curve assess diagnostic value, CIBERSORT analysed immune cell infiltration. We identified 20 intersecting among DEGs of OA, key module MetS, ARGs. By comparing accuracy four models for disease prediction, SVM model, which includes CEBPB, PTEN, ARPC1B, PIK3R1, CDC42, selected. These hub ARGs not only demonstrated strong values based on data but also exhibited a significant correlation Building these findings, we have five that are associated infiltration constructed at early diagnosing

Language: Английский

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Vascular and Metabolic Responses to Elevated Circulating PDGF-BB in Mice: A Multiparametric MRI Study

Published: April 2, 2025

Article Vascular and Metabolic Responses to Elevated Circulating PDGF-BB in Mice: A Multiparametric MRI Study Xiuli Yang 1,†, Jiekang Wang 2,3,†, Yuguo Li 1,4, Mei Wan 2,3,*, Zhiliang Wei 1,4,* 1 Russell H. Morgan Department of Radiology Radiological Science, Johns Hopkins University School Medicine, Baltimore, MD 21205, USA 2 Orthopaedic Surgery, 3 Biomedical Engineering, 4 F. M. Kirby Research Center for Functional Brain Imaging, Kennedy Krieger Institute, * Correspondence: [email protected] (M.W.); [email protected] (Z.W.) † These authors contributed equally this work. Received: 20 November 2024; Revised: December Accepted: 22 January 2025; Published: 11 February 2025 Abstract: circulating platelet-derived growth factor-BB (PDGF-BB) has been implicated the development various aged-related pathologies is recognized as a potential pro-aging factor. Although numerous studies have explored pathological roles PDGF-BB/PDGFRβ signaling pathway, few investigations dissected its function neurofunctional responses elevated PDGF-BB, primarily because in-vivo measurements are generally required assess neurofunction. To address knowledge gap, we characterized vascular metabolic vivo using multiparametric non-invasive non-contrast techniques conditional Pdgfb transgenic mouse model (PdgfbcTG) at 6 months age. Results indicated that PdgfbcTG mice exhibited decreased cerebral blood flow (p = 0.025), oxygen extraction 0.002), increased rate 0.035), mirroring changes observed human aging. The change was significantly higher (≥200.3%) compared naturally aged mice. This study provides evidence accelerates neurovascular

Language: Английский

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Cellular Senescence: The Driving Force of Musculoskeletal Diseases

Biomedicines, Journal Year: 2024, Volume and Issue: 12(9), P. 1948 - 1948

Published: Aug. 26, 2024

The aging of the world population is closely associated with an increased prevalence musculoskeletal disorders, such as osteoporosis, sarcopenia, and osteoarthritis, due to common genetic, endocrine, mechanical risk factors. These conditions are characterized by degeneration bone, muscle, cartilage tissue, resulting in fractures reduced mobility. Importantly, a crucial role pathophysiology these diseases has been proposed for cellular senescence, state irreversible cell cycle arrest induced factors DNA damage, telomere shortening, mitochondrial dysfunction. In addition, senescent cells secrete pro-inflammatory molecules, called senescence-associated secretory phenotype (SASP), which can alter tissue homeostasis promote disease progression. Undoubtedly, targeting their profiles could development integrated strategies, including regular exercise balanced diet or use senolytics senomorphs, improve quality life population. Therefore, our review aimed highlight senescence age-related diseases, summarizing main underlying mechanisms potential anti-senescence strategies treatment osteoarthritis.

Language: Английский

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Disturbed glycolipid metabolism activates CXCL13-CXCR5 axis in senescent TSCs to promote heterotopic ossification

Cellular and Molecular Life Sciences, Journal Year: 2024, Volume and Issue: 81(1)

Published: June 17, 2024

Heterotopic ossification (HO) occurs as a common complication after injury, while its risk factor and mechanism remain unclear, which restricts the development of pharmacological treatment. Clinical research suggests that diabetes mellitus (DM) patients are prone to developing HO in tendon, but solid evidence mechanical still needed. Here, we combined clinical samples DM mice model identify disordered glycolipid metabolism aggravates senescence tendon-derived stem cells (TSCs) promotes osteogenic differentiation. Then, combining RNA-seq results aging detected abnormally activated autocrine CXCL13-CXCR5 axis TSCs cultured high fat, glucose (HFHG) environment also aged tendon. Genetic inhibition CXCL13 successfully alleviated formation mice, providing potential therapeutic target for suppressing trauma or surgery.

Language: Английский

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Research progress on interferon and cellular senescence

The FASEB Journal, Journal Year: 2024, Volume and Issue: 38(16)

Published: Aug. 19, 2024

Abstract Since the 12 major signs of aging were revealed in 2023, people's interpretation will go further, which is great significance for understanding occurrence, development, and intervention process. As one aging, cellular senescence refers to process proliferation differentiation ability cells decrease under stress stimulation or over time, often manifested as changes cell morphology, cycle arrest, decreased metabolic function. Interferon (IFN), a secreted ligand specific surface receptors, can trigger transcription interferon‐stimulated genes (ISGs) play an important role senescence. In addition, IFN serves component SASP, activation signaling pathway has been shown contribute apoptosis It expected delay by linking with studying effects on its mechanism. This article provides review research relationship between consulting relevant literature.

Language: Английский

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Osteoporosis induced by cellular senescence: A mathematical model

PLoS ONE, Journal Year: 2024, Volume and Issue: 19(5), P. e0303978 - e0303978

Published: May 28, 2024

Osteoporosis is a disease characterized by loss of bone mass, where bones become fragile and more likely to fracture. Bone density begins decrease at age 50, state osteoporosis defined than 25%. Cellular senescence permanent arrest normal cell cycle, while maintaining viability. The number senescent cells increase with age. Since an aging disease, it natural consider the question what extend induce osteoporosis. In this paper we use mathematical model address question. We determine percent for men women during 50 100 years, results depend on rate η net formation cell, = 1 being average rate. case 1, simulations are in agreement empirical data. also senolytic drugs, like fisetin quercetin, that selectively eliminate cells, assess their efficacy terms reducing loss. For example, estrogen hormonal therapy early treatment fisetin, 75 23.4% (below osteoporosis), no 25.8% (osteoporosis); without even therapy, 25.3% occurs already 65.

Language: Английский

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Clock gene Bmal1 influences the cell cycle of chondrocytes in osteoarthritis

Research Square (Research Square), Journal Year: 2024, Volume and Issue: unknown

Published: Sept. 26, 2024

Osteoarthritis (OA) is a degenerative disease caused by multiple factors. This study used in vitro and animal models to investigate the connection between biological clock cell cycle osteoarthritic cartilage. The results indicate that transcription levels of circadian gene Bmal1 exhibit negative correlation with Mmp13 positive Wee1. Thus, increased expression Wee1 may be potential protective factor osteoarthritis, while high Per1, Cdk1, Ccnb1, risk factor. By controlling contributing pathophysiology OA, impact apoptosis chondrocytes.

Language: Английский

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The Skeleton as a Secretory Organ

Calcified Tissue International, Journal Year: 2023, Volume and Issue: 113(1), P. 1 - 3

Published: July 1, 2023

Language: Английский

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