Mitochondrial dysfunction and therapeutic perspectives in osteoporosis

Frontiers in Endocrinology, Год журнала: 2024, Номер 15

Опубликована: Фев. 2, 2024

Osteoporosis (OP) is a systemic skeletal disorder characterized by reduced bone mass and structural deterioration of tissue, resulting in heightened vulnerability to fractures due increased fragility. This condition primarily arises from an imbalance between the processes resorption formation. Mitochondrial dysfunction has been reported potentially constitute one most crucial mechanisms influencing pathogenesis osteoporosis. In essence, mitochondria play role maintaining delicate equilibrium formation resorption, thereby ensuring optimal health. Nevertheless, disruption this balance can arise as consequence mitochondrial dysfunction. dysfunctional mitochondria, electron transport chain (ETC) becomes uncoupled, ATP synthesis generation reactive oxygen species (ROS). Reinforcement further exacerbated accumulation aberrant mitochondria. review, we investigated analyzed correlation dysfunction, encompassing DNA (mtDNA) alterations, oxidative phosphorylation (OXPHOS) impairment, mitophagy dysregulation, defects biogenesis dynamics, well excessive ROS accumulation, with regards OP ( Figure 1 ). Furthermore, explore prospective strategies currently available for modulating ameliorate Undoubtedly, certain therapeutic still require investigation ensure their safety efficacy clinical treatments. However, perspective, potential establishing effective safe approaches osteoporosis appears promising.

Язык: Английский

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Cellular senescence in skeletal disease: mechanisms and treatment

Cellular & Molecular Biology Letters, Год журнала: 2023, Номер 28(1)

Опубликована: Окт. 27, 2023

Abstract The musculoskeletal system supports the movement of entire body and provides blood production while acting as an endocrine organ. With aging, balance bone homeostasis is disrupted, leading to loss degenerative diseases, such osteoporosis, osteoarthritis, intervertebral disc degeneration. Skeletal diseases have a profound impact on motor cognitive abilities elderly, thus creating major challenge for both global health economy. Cellular senescence caused by various genotoxic stressors results in permanent cell cycle arrest, which considered be underlying mechanism aging. During senescent cells (SnCs) tend aggregate trigger chronic inflammation releasing senescence-associated secretory phenotypic factors. Multiple signalling pathways are involved regulating cellular marrow microenvironments. Targeted SnCs alleviate age-related diseases. However, association between remains unclear. This review summarises fundamental role skeletal highlights that mediate senescence, discusses potential therapeutic strategies targeting SnCs. Graphical

Язык: Английский

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Regulation Mechanisms and Maintenance Strategies of Stemness in Mesenchymal Stem Cells

Stem Cell Reviews and Reports, Год журнала: 2023, Номер 20(2), С. 455 - 483

Опубликована: Ноя. 27, 2023

Язык: Английский

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Impact of miR-214-5p and miR-21-5p from hypoxic endometrial exosomes on human umbilical cord mesenchymal stem cell function

World Journal of Stem Cells, Год журнала: 2025, Номер 17(2)

Опубликована: Фев. 24, 2025

Exosomes derived from hypoxic endometrial epithelial cells are pivotal in cellular communication and tissue repair, offering new perspectives on reproductive health. This manuscript highlights the study by Zhang et al, which investigates effects of miR-214-5p miR-21-5p cell-derived exosomes human umbilical cord mesenchymal stem cells. The reveals that low levels these microRNAs activate signal transducer activator transcription 3 signaling pathway, enhancing cell migration differentiation. These findings provide novel insights into therapeutic strategies for improving health addressing infertility linked to thin endometrium.

Язык: Английский

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DNA Tetrahedron Delivering miR‐21‐5p Promotes Senescent Bone Defects Repair through Synergistic Regulation of Osteogenesis and Angiogenesis

Advanced Healthcare Materials, Год журнала: 2024, Номер unknown

Опубликована: Июль 9, 2024

Abstract Compromised osteogenesis and angiogenesis is the character of stem cell senescence, which brought difficulties for bone defects repairing in senescent microenvironment. As most abundant bone‐related miRNA, miRNA‐21‐5p plays a crucial role inducing osteogenic angiogenic differentiation. However, highly efficient miR‐21‐5p delivery still confronts challenges including poor cellular uptake easy degradation. Herein, TDN‐miR‐21‐5p nanocomplex constructed based on DNA tetrahedral (TDN) has great potential promoting alleviating senescence marrow cells (O‐BMSCs), simultaneously enhancing capacity endothelial progenitor (O‐EPCs). Of note, activation AKT Erk signaling pathway may direct regulatory mechanism mediated O‐BMSCs. Also, can indirectly mediate O‐BMSCs through pro‐angiogenic growth factors secreted from O‐EPCs. In addition, gelatin methacryloyl (GelMA) hydrogels are mixed with TDN to fabricate scaffolds. TDN‐miR‐21‐5p@GelMA scaffold exhibits greater repair increased expression osteogenic‐ angiogenic‐related markers critical‐size cranial vivo. Collectively, alleviate induce microenvironment, provides novel candidate strategy widen clinical application TDNs‐based gene therapy.

Язык: Английский

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The role of WWP1 and WWP2 in bone/cartilage development and diseases

Molecular and Cellular Biochemistry, Год журнала: 2024, Номер unknown

Опубликована: Янв. 22, 2024

Язык: Английский

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Rejuvenation of Bone Marrow Mesenchymal Stem Cells: Mechanisms and Their Application in Senile Osteoporosis Treatment

Biomolecules, Год журнала: 2025, Номер 15(2), С. 276 - 276

Опубликована: Фев. 13, 2025

Bone marrow mesenchymal stromal cells (BM-MSCs) are multipotent present in bone marrow; they play a crucial role the process of formation. Cellular senescence is defined as stable state cell cycle arrest that impairs functioning cells. Research has shown aging triggers BM-MSCs, leading to reduced capacity for osteogenic differentiation and accumulation senescent cells, which can accelerate onset various diseases. Therefore, it essential explore mechanisms strategies rejuvenation BM-MSCs. Senile osteoporosis (SOP) metabolic disease characterized by The BM-MSCs considered one most important factors occurrence development SOP. treatment SOP represents promising strategy. This work provides summary functional alterations observed systematic review facilitate Additionally, we analyze progress limitations associated with application rejuvenated treat SOP, aim providing new insights prevention

Язык: Английский

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A galactose-tethered tetraphenylethene prodrug mediated apoptosis of senescent cells for osteoporosis treatment

Science Advances, Год журнала: 2025, Номер 11(8)

Опубликована: Фев. 19, 2025

Osteoporosis and bone injury healing in elderly patients are major medical challenges, often exacerbated by the accumulation of senescent cells. Herein, we show that TPE-Gal, which contains a tetraphenylethene unit galactose moiety, offers promising molecular therapy designed to light up eliminate cells through hydrolysis reaction catalyzed β-galactosidase, an enzyme overexpressed The produces TPE-OH, which, turn, increases reactive oxygen species levels within cells, leading noninflammatory apoptosis This targeted clearance mechanism helps alleviate osteoporosis symptoms promotes healing. Moreover, apoptotic vesicles, generated during process, partly phagocytosed macrophages, mimicking physiological metabolic processes. study opens new avenues for addressing health issues bioclearance aligning with body’s natural pathways maintaining homeostasis.

Язык: Английский

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Cardiac-specific overexpression of serum response factor regulates age-associated decline in mitochondrial function

GeroScience, Год журнала: 2025, Номер unknown

Опубликована: Март 31, 2025

Язык: Английский

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MiR-144-5p and miR-21-5p do not drive bone disease in a mouse model of type 1 diabetes mellitus

JBMR Plus, Год журнала: 2024, Номер 8(5)

Опубликована: Март 28, 2024

Abstract The increased risk of fractures in patients with type 1 diabetes mellitus (T1DM) is nowadays well recognized. However, the exact mechanism action diabetic bone disease has not been fully elucidated. MicroRNAs (miRNAs) are gene regulators that operate post-transcriptionally and have implicated development various metabolic disorders including T1DM. Previous studies a role for miR-144-5p miR-21-5p, which involved controlling oxidative stress by targeting Nrf2, To date, it unclear whether miR-21-5p affect health Thus, this study aimed to investigate influence knockdown T1DM male mice. Therefore, was induced 10-wk-old mice using streptozotocin (STZ). One week later, after hyperglycemia, antagomir-144-5p antagomir-21-5p or their non-targeting control were administered at 10 mg/kg BW once until end experiment. At 14 wk age, glucose levels, bone, fat mass analyzed. results revealed treating did protect against loss, despite successful downregulation miRNAs normalization Nrf2 mRNA levels tissue. Histological serological parameters formation resorption altered antagomir treatment. Finally, we measured expression miRNA-144-5p miRNA-21-5p serum 30 individuals compared them non-diabetic controls, but find an either miRNA. In conclusion, does STZ-induced loss normalize anti-oxidant factor

Язык: Английский

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