Dexamethasone Induced Osteocyte Apoptosis in Steroid‐Induced Femoral Head Osteonecrosis through ROS‐Mediated Oxidative Stress DOI Creative Commons
Xinglong Zhang,

Zhenhuan Yang,

Qian Xu

et al.

Orthopaedic Surgery, Journal Year: 2024, Volume and Issue: 16(3), P. 733 - 744

Published: Feb. 21, 2024

Objective Glucocorticoid (GC) overuse is strongly associated with steroid‐induced osteonecrosis of the femoral head (SINFH). However, underlying mechanism SINFH remains unclear. This study aims to investigate effect dexamethasone (Dex)‐induced oxidative stress on osteocyte apoptosis and mechanisms. Methods Ten patients 10 developmental dysplasia hips (DDH) were enrolled in our study. Sixty rats randomly assigned Control, Dex, Dex + N‐Acetyl‐L‐cysteine (NAC), Dibenziodolium chloride (DPI), NAC, DPI groups. Magnetic resonance imaging (MRI) was used examine edema rats. Histopathological staining performed assess osteonecrosis. Immunofluorescence TUNEL 8‐OHdG conducted evaluate damage. Immunohistochemical carried out detect expression NOX1, NOX2, NOX4. Viability MLO‐Y4 cells measured using CCK‐8 assay staining. stress. 2′,7′‐Dichlorodihydrofluorescein diacetate (DCFH‐DA) measure reactive oxygen species (ROS). The NOX4 analyzed by Western blotting. Multiple comparisons one‐way analysis variance (ANOVA). Results In rat model, hematoxylin–eosin (HE) revealed a significantly higher rate empty lacunae group than DDH group. indicated significant increase TUNEL‐positive 8‐OHdG‐positive compared demonstrated proteins patients. Moreover, immunohistochemical showed proportion NOX2‐positive Control vitro, inhibited viability induced apoptosis. After treatment, intracellular ROS level increased. treatment did not alter NOX vitro. Additionally, NAC generation partially alleviated vivo Conclusion demonstrates that GC promotes through ROS‐induced Furthermore, we found increased NOXs serves as an important source generation.

Language: Английский

Oxidative Stress and Inflammation in Osteoporosis: Molecular Mechanisms Involved and the Relationship with microRNAs DOI Open Access
Teresa Iantomasi, Cecilia Romagnoli, Gaia Palmini

et al.

International Journal of Molecular Sciences, Journal Year: 2023, Volume and Issue: 24(4), P. 3772 - 3772

Published: Feb. 14, 2023

Osteoporosis is characterized by the alteration of bone homeostasis due to an imbalance between osteoclastic resorption and osteoblastic formation. Estrogen deficiency causes loss postmenopausal osteoporosis, pathogenesis which also involves oxidative stress, inflammatory processes, dysregulation expression microRNAs (miRNAs) that control gene at post-transcriptional levels. Oxidative increase in reactive oxygen species (ROS), proinflammatory mediators altered levels miRNAs enhance osteoclastogenesis reduce osteoblastogenesis through mechanisms involving activation MAPK transcription factors. The present review summarizes principal molecular involved role ROS cytokines on osteoporosis. Moreover, it highlights interplay among miRNA levels, state. In fact, ROS, activating transcriptional factors, can affect expression, regulate production processes. Therefore, should help identifying targets for development new therapeutic approaches osteoporotic treatment improve quality life patients.

Language: Английский

Citations

150
The Nrf2 antioxidant defense system in intervertebral disc degeneration: Molecular insights DOI Creative Commons
Qian Xiang, Yongzhao Zhao, Jialiang Lin

et al.

Experimental & Molecular Medicine, Journal Year: 2022, Volume and Issue: 54(8), P. 1067 - 1075

Published: Aug. 17, 2022

Intervertebral disc degeneration (IDD) is a common degenerative musculoskeletal disorder and recognized as major contributor to discogenic lower back pain. However, the molecular mechanisms underlying IDD remain unclear, therapeutic strategies for are currently limited. Oxidative stress plays pivotal roles in pathogenesis progression of many age-related diseases humans, including IDD. Nuclear factor E2-related 2 (Nrf2) master antioxidant transcription that protects cells against oxidative damage. Nrf2 negatively modulated by Kelch-like ECH-associated protein 1 (Keap1) exerts important effects on progression. Accumulating evidence has revealed can facilitate downstream genes binding response elements (AREs) promoter regions, heme oxygenase-1 (HO-1), glutathione (GSH), superoxide dismutase (SOD), catalase (CAT), NADPH quinone dehydrogenase (NQO1). The defense system regulates cell apoptosis, senescence, extracellular matrix (ECM) metabolism, inflammatory nucleus pulposus (NP), calcification cartilaginous endplates (EP) In this review, we aim discuss current knowledge systematically.

Language: Английский

Citations

99
Oxidative Stress and Natural Antioxidants in Osteoporosis: Novel Preventive and Therapeutic Approaches DOI Creative Commons
Gemma Marcucci, Vladana Domazetovic, Chiara Nediani

et al.

Antioxidants, Journal Year: 2023, Volume and Issue: 12(2), P. 373 - 373

Published: Feb. 3, 2023

This review reports in detail the cellular and molecular mechanisms which regulate bone remodeling process relation to oxidative stress (OS), inflammatory factors, estrogen deficiency. OS is considered an important pathogenic factor of osteoporosis, inducing osteocyte apoptosis varying levels specific such as receptor activator κB ligand (RANKL), sclerostin, and, according recent evidence, fibroblast growth 23, with consequent impairment high resorption. Bone loss increases risk fragility fractures, most commonly used treatments are antiresorptive drugs, followed by anabolic drugs or those a double effect. In addition, data show that natural antioxidants contained diet efficient preventing reducing negative effects on osteocytes through involvement sirtuin type 1 enzyme. Indeed, some their factors potential biological targets can act prevent reduce loss, well promote regenerative processes restoring physiological remodeling. Several suggest including novel therapeutic approaches develop better management strategies for prevention treatment osteoporosis OS-related diseases. particular, anthocyanins, resveratrol, lycopene, oleuropein, vitamins, thiol antioxidants, could have protective anti-osteoporotic effects.

Language: Английский

Citations

90
The role of oxidative stress in the development of knee osteoarthritis: A comprehensive research review DOI Creative Commons
Lin Liu, Pan Luo, Mingyi Yang

et al.

Frontiers in Molecular Biosciences, Journal Year: 2022, Volume and Issue: 9

Published: Sept. 20, 2022

Knee osteoarthritis (KOA) is one of the most common degenerative diseases, and its core feature degeneration damage articular cartilage. The cartilage KOA due to destruction dynamic balance caused by activation chondrocytes various factors, with oxidative stress playing an important role in pathogenesis KOA. overproduction reactive oxygen species (ROS) a result stress, which redox process that goes awry inherent antioxidant defence system human body. Superoxide dismutase (SOD) inside outside plays key regulating ROS Additionally, synovitis factor development In inflammatory environment, hypoxia synovial cells leads mitochondrial damage, increase levels, further aggravates synovitis. addition, significantly accelerates telomere shortening ageing chondrocytes, while promotes KOA, damages regulation mitochondria cartilage, stimulates production aggravate At present, there are many drugs regulate level ROS, but these still need be developed verified animal models We discuss mainly how part Although current research has achieved some results, more needed.

Language: Английский

Citations

84
miRNAs as potential game-changers in bone diseases: Future medicinal and clinical uses DOI
Ahmed S. Doghish, Mohammed S. Elballal, Ola Elazazy

et al.

Pathology - Research and Practice, Journal Year: 2023, Volume and Issue: 245, P. 154440 - 154440

Published: April 6, 2023

Language: Английский

Citations

54
Luteolin rescues postmenopausal osteoporosis elicited by OVX through alleviating osteoblast pyroptosis via activating PI3K-AKT signaling DOI Creative Commons
Shuang Chai, Yanbing Yang, Liwei Wei

et al.

Phytomedicine, Journal Year: 2024, Volume and Issue: 128, P. 155516 - 155516

Published: March 16, 2024

Recently, osteoblast pyroptosis has been proposed as a potential pathogenic mechanism underlying osteoporosis, although this remains to be confirmed. Luteolin (Lut), flavonoid phytochemical, plays critical role in the anti-osteoporosis effects of many traditional Chinese medicine prescriptions. However, its protective impact on osteoblasts postmenopausal osteoporosis (PMOP) not elucidated. This research aimed determine effect Lut ameliorating PMOP by alleviating and sustaining osteogenesis. was designed investigate novel both cell animal models. Ovariectomy-induced models were established mice with/without daily gavaged 10 or 20 mg/kg body weight Lut. The bone microstructure, metabolism oxidative stress evaluated with 0.104 Estradiol Valerate Tablets positive control. Network pharmacological analysis molecular docking employed mechanisms treatment. Subsequently, impacts PI3K/AKT axis, stress, mitochondria, assessed. In vitro, cultured (MC3T3-E1(14) cells exposed H2O2 examine signaling pathway, osteogenic differentiation, mitochondrial function, pyroptosis. Our findings demonstrated that Lut, similar control drug, effectively reduced systemic loss enhanced induced ovariectomy. indicated axis target, response nuclear membrane function being key mechanisms. Consequently, investigated. vivo data revealed deactivated following ovariectomy, restored phosphorylation proteins, thereby reactivating axis. Additionally, alleviated abnormalities intervention mitigated inhibition osteogenesis, well H2O2-induced Furthermore, attenuated ROS accumulation dysfunction. including osteogenesis restoration, anti-pyroptosis, maintenance, all reversed LY294002 (a pathway inhibitor). summary, could improve dysfunction, alleviate GSDME-mediated maintain via activating PI3K/Akt offering new therapeutic strategy for PMOP.

Language: Английский

Citations

21
Serum Uric Acid and Bone Health in Middle-Aged and Elderly Hypertensive Patients: A Potential U-Shaped Association and Implications for Future Fracture Risk DOI Creative Commons
Shuaiwei Song, Xintian Cai,

Junli Hu

et al.

Metabolites, Journal Year: 2025, Volume and Issue: 15(1), P. 15 - 15

Published: Jan. 3, 2025

The influence of serum uric acid (SUA) on bone metabolism, as suggested by previous studies, remains a contentious issue. SUA plays complex role in health and hypertension, making it challenging to discern its impact the skeletal status middle-aged elderly hypertensive patients. This study aims elucidate effects health, with particular focus association osteoporosis risk fractures. Multiple linear regression analyzed levels against mineral density (BMD) future fracture risk. Additionally, multivariate logistic was used examine between osteoporosis. Dose-response relationship analysis conducted using generalized smooth curve fitting (GSCF) restricted cubic spline (RCS) methods. With exception total femur region, BMD showed positive connection. GSCF revealed an inverted U-shaped BMD, alongside trend FRAX scores. Moreover, RCS indicated levels, higher risks identified first third tertiles compared second tertile. In individuals older is substantially linked health. identification relationships scores highlights nuanced SUA. These findings suggest that both low high may adversely affect emphasizing need for further research.

Language: Английский

Citations

3
Application and progress of 3D printed biomaterials in osteoporosis DOI Creative Commons
Chenxu Wang, Aiguo Liu, Ziwen Zhao

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2025, Volume and Issue: 13

Published: Feb. 4, 2025

Osteoporosis results from a disruption in skeletal homeostasis caused by an imbalance between bone resorption and formation. Conventional treatments, such as pharmaceutical drugs hormone replacement therapy, often yield suboptimal are frequently associated with side effects. Recently, biomaterial-based approaches have gained attention promising alternatives for managing osteoporosis. This review summarizes the current advancements 3D-printed biomaterials designed osteoporosis treatment. The benefits of compared to traditional systemic drug therapies discussed. These materials can be broadly categorized based on their functionalities, including promoting osteogenesis, reducing inflammation, exhibiting antioxidant properties, inhibiting osteoclast activity. 3D printing has advantages speed, precision, personalization, etc. It is able satisfy requirements irregular geometry, differentiated composition, multilayered structure articular osteochondral scaffolds boundary layer structure. limitations existing critically analyzed future directions considered.

Language: Английский

Citations

2
VDR activation attenuates osteoblastic ferroptosis and senescence by stimulating the Nrf2/GPX4 pathway in age-related osteoporosis DOI

Pingcui Xu,

Bingfeng Lin,

Xuehui Deng

et al.

Free Radical Biology and Medicine, Journal Year: 2022, Volume and Issue: 193, P. 720 - 735

Published: Nov. 1, 2022

Language: Английский

Citations

63
Prussian blue nanozymes: progress, challenges, and opportunities DOI
Hongliang He, Mengmeng Long, Yifan Duan

et al.

Nanoscale, Journal Year: 2023, Volume and Issue: 15(31), P. 12818 - 12839

Published: Jan. 1, 2023

Prussian Blue Nanozymes (PBNZs) have emerged as highly efficient agents for reactive oxygen species (ROS) elimination, owing to their multiple enzyme-like properties encompassing catalase (CAT), peroxidase (POD), and superoxide dismutase (SOD) activities. As a functional nanomaterial mimicking enzyme, PBNZs not only surmount the limitations of natural enzymes, such instability high manufacturing costs, but also exhibit superior stability, tunable activity, low storage expenses, remarkable reusability. Consequently, gained significant attention in diverse biomedical applications, including disease diagnosis therapy. Over past decade, propelled by advancements catalysis science, biotechnology, computational nanotechnology, witnessed progress exploration enzymatic activities, elucidation catalytic mechanisms, wide-ranging applications. This comprehensive review aims provide systematic overview discovery mechanisms PBNZ, along with strategies employed modulate Furthermore, we extensively survey recent utilizing scavenging ROS various Lastly, analyze existing challenges translating into therapeutic clinical use outline future research directions this field. By presenting synopsis current state knowledge, seeks contribute deeper understanding immense potential an innovative agent biomedicine.

Language: Английский

Citations

36