GSK-3β suppression upregulates Gli1 to alleviate osteogenesis inhibition in titanium nanoparticle-induced osteolysis DOI Creative Commons
Qing Wang, Wei Zhang, Xiaole Peng

et al.

Journal of Nanobiotechnology, Journal Year: 2022, Volume and Issue: 20(1)

Published: March 19, 2022

Wear particle-induced periprosthetic osteolysis (PPO) have become a major reason of joint arthroplasty failure and secondary surgery following thus pose severe threat to global public health. Therefore, determining how effectively suppress PPO has an urgent problem. The pathological mechanism involved in the signaling cascade is still unclear. Recently, interaction between osteogenic inhibition wear particles at implant biological interface, which received increasing attention, been revealed as important factor process. Additionally, Hedgehog (Hh)-Gli1 crucial was regulated by multiple factors numerous physiological It exert part during embryonic bone development metabolism. However, whether Hh-Gli1 remains unknown. Our present study explored regulates titanium (Ti) nanoparticle-induced osteolysis. We found that dramatically downregulated upon Ti particle treatment. Mechanistically, glycogen synthesis kinase 3β (GSK-3β) activation significantly increased via changes GSK-3β phosphorylation level participate posttranslational modification degradation key transcription Gli1, decreasing accumulation Gli1 its translocation from cytoplasm nucleus. Collectively, these findings suggest utilizes GSK3β-mediated may serve rational new therapeutic target against PPO.

Language: Английский

Hedgehog signalling in bone and osteoarthritis: the role of Smoothened and cholesterol DOI
Abbi E. Smith, Elín Sóley Sigurbjörnsdóttir, Eirı́kur Steingrı́msson

et al.

FEBS Journal, Journal Year: 2022, Volume and Issue: 290(12), P. 3059 - 3075

Published: March 19, 2022

Hedgehog signalling is essential for development, crucial normal anatomical arrangement and activated during tissue damage repair. Dysregulation of hedgehog associated with cancer, developmental disorders other diseases including osteoarthritis (OA). The gene was first discovered in Drosophila melanogaster, the pathway evolutionarily conserved most animals. Although there are several ligands different protein expression patterns, they share a common plasma membrane receptor, Patched1 activation transduced through G-protein-coupled receptor-like Smoothened (SMO) downstream effectors. Functional assays revealed that SMO dependent on sterol binding, cholesterol observed bound to crystallography experiments. In vertebrates, coordinates endochondral ossification balances osteoblast osteoclast maintain homeostasis. A recently mutation humans (SMOR173C ) predicted alter binding higher risk hip OA. studies mice human analysis provide evidence pathologically chondrocytes osteoarthritic cartilage.

Language: Английский

Citations

17
Roles of extracellular vesicles in periodontal homeostasis and their therapeutic potential DOI Creative Commons
Dao‐Kun Deng,

Jiu-Jiu Zhang,

Dian Gan

et al.

Journal of Nanobiotechnology, Journal Year: 2022, Volume and Issue: 20(1)

Published: Dec. 30, 2022

Abstract Periodontal tissue is a highly dynamic and frequently stimulated area where homeostasis easily destroyed, leading to proinflammatory periodontal diseases. Bacteria–bacteria cell–bacteria interactions play pivotal roles in disease progression. Several reviews have comprehensively summarized the of bacteria stem cells homeostasis. However, they did not describe extracellular vesicles (EVs) from cells. As communication mediators evolutionarily conserved eukaryotic cells, EVs secreted by or can mediate between their hosts, thereby offering great promise for maintenance This review offers an overview EV biogenesis, effects on homeostasis, recent advances EV-based regenerative strategies. Specifically, we document pathogenic bacteria-derived (BEVs) dyshomeostasis, focusing plaque biofilm formation, immune evasion, inflammatory pathway activation destruction. Moreover, summarize advancements cell-derived (CEVs) emphasizing multifunctional biological CEVs regeneration. Finally, discuss future challenges practical perspectives clinical translation therapies periodontitis. Graphical

Language: Английский

Citations

17
Signaling pathway mechanisms of circadian clock gene Bmal1 regulating bone and cartilage metabolism: a review DOI Creative Commons

Yiting Ze,

WU Yong-yao,

Zhen Tan

et al.

Bone Research, Journal Year: 2025, Volume and Issue: 13(1)

Published: Jan. 27, 2025

Abstract Circadian rhythm is ubiquitous in nature. clock genes such as Bmal1 and Clock form a multi-level transcription-translation feedback network, regulate variety of physiological pathological processes, including bone cartilage metabolism. Deletion the core gene leads to alterations, while phenotypes are not consistent. Studies have shown that multiple signaling pathways involved process regulating metabolism, but exact regulatory mechanisms remain unclear. This paper reviews by which regulates bone/cartilage upstream factors control , current knockout mouse models for research. We hope provide new insights prevention treatment diseases related circadian rhythms.

Language: Английский

Citations

0
Signaling Pathways Driving MSC Osteogenesis: Mechanisms, Regulation, and Translational Applications DOI Open Access
Liuqing Wang,

M.Q. Ruan,

Qiqi Bu

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(3), P. 1311 - 1311

Published: Feb. 4, 2025

Mesenchymal stem cells (MSCs) are crucial for skeletal development, homeostasis, and repair, primarily through their differentiation into osteoblasts other lineage cells. Key signaling pathways, including Wnt, TGF-β/BMP, PTH, Hedgehog, IGF, act as critical regulators of MSC osteogenesis, playing pivotal roles in maintaining bone homeostasis facilitating regeneration. These pathways interact distinct ways at various stages mineralization, remodeling. This review provides an overview the molecular mechanisms by which these regulate influence on tissue formation, implications diseases therapeutic strategies. Additionally, we explore potential applications engineering, with a particular focus promoting use MSCs seed defect repair. Ultimately, this aims to highlight avenues advancing biology research, treating disorders, enhancing regenerative medicine.

Language: Английский

Citations

0
Predicting pathogenic variants in the IHH gene associated with bone development abnormalities: a bioinformatics approach DOI Creative Commons

Swetha Sunkar,

G. Pavankumar,

Vignesh Hariharan

et al.

Deleted Journal, Journal Year: 2025, Volume and Issue: 2(1)

Published: April 14, 2025

Abstract Bone development abnormalities are challenging disorders with significant physical and emotional impacts. These can stem from genetic or lifestyle factors, causes presenting ongoing research challenges. This study investigates the Indian hedgehog (Ihh) gene, which is known to be involved in bone formation issues. We analyzed non-synonymous single nucleotide polymorphisms (nsSNPs) Ihh gene retrieved dbSNP database for their deleterious nature functional impact using various programs, including PolyPhen-2.0, FATHMM, Panther, SIFT, Provean, Mutation Assessor, SNPS&GO. The stability of protein structure was evaluated Dynamut I-Mutant 3.0. Out 436 nsSNPs analyzed, 103 mutations were found destabilize protein. Special attention given located domain regions critical function. Native mutant models predicted SWISSMODEL, validated PROCHECK, compared RMSD values PyMOL. Functional impacts assessed through docking studies binding partner PatchDock. Significant changes interaction energies scores observed, suggesting potential effects on computational indicates that these may contribute bone-related suggests could a drug target further investigation improved disease management.

Language: Английский

Citations

0
Mechanisms of bone regeneration repair and potential and efficacy of small molecule drugs DOI
Ke Zhang,

Hao Li,

Tao Wang

et al.

Biomedicine & Pharmacotherapy, Journal Year: 2025, Volume and Issue: 187, P. 118070 - 118070

Published: April 21, 2025

Language: Английский

Citations

0
Research progress of functional motifs based on growth factors in cartilage tissue engineering: A review DOI Creative Commons
Shengao Qin,

Jiaman Zhu,

Guangyong Zhang

et al.

Frontiers in Bioengineering and Biotechnology, Journal Year: 2023, Volume and Issue: 11

Published: Feb. 7, 2023

Osteoarthritis is a chronic degenerative joint disease that exerts significant impacts on personal life quality, and cartilage tissue engineering practical treatment in clinical. Various growth factors are involved regeneration play important roles therein, which the focus of current repair strategy. To compensate for purification difficulty, high cost, poor metabolic stability, circulating dilution natural factors, concept functional motifs (also known as mimetic peptides) from original factor was introduced recent studies. Here, we reviewed selection mechanisms, biological functions, carrier scaffolds, modification methods factor-related motifs, evaluated performance engineering. Finally, prospects researches clinical application were discussed.

Language: Английский

Citations

9
A Janus, robust, biodegradable bacterial cellulose/Ti3C2Tx MXene bilayer membranes for guided bone regeneration DOI

Hongling Zhou,

Yifan Zhao, Xiang‐Jun Zha

et al.

Biomaterials Advances, Journal Year: 2024, Volume and Issue: 161, P. 213892 - 213892

Published: May 11, 2024

Language: Английский

Citations

3
IRE1α pathway: A potential bone metabolism mediator DOI Creative Commons

Chengbo Yu,

Zhixiang Zhang, Li Xiao

et al.

Cell Proliferation, Journal Year: 2024, Volume and Issue: 57(10)

Published: May 12, 2024

Abstract Osteoblasts and osteoclasts collaborate in bone metabolism, facilitating development, maintaining normal density strength, aiding the repair of pathological damage. Endoplasmic reticulum stress (ERS) can disrupt intracellular equilibrium between osteoclast osteoblast, resulting dysfunctional metabolism. The inositol‐requiring enzyme‐1α (IRE1α) pathway—the most conservative unfolded protein response pathway activated by ERS—is crucial regulating cell This involvement encompasses functions such as inflammation, autophagy, apoptosis. Many studies have highlighted potential roles IRE1α osteoblasts, chondrocytes, its implication certain bone‐related diseases. These findings suggest that it may serve a mediator for However, relevant reviews on role metabolism remain unavailable. Therefore, this review aims to explore recent research elucidated intricate specifically osteogenesis, chondrogenesis, osteoclastogenesis, osteo‐immunology. provide novel insights into treating

Language: Английский

Citations

3
Exploring of exosomes in pathogenesis, diagnosis and therapeutic of osteonecrosis of the femoral head: the mechanisms and signaling pathways DOI

Sheqing Chen,

Jin Liu,

Nuoya Zhang

et al.

Biomedical Materials, Journal Year: 2024, Volume and Issue: 19(5), P. 052006 - 052006

Published: Aug. 9, 2024

Osteonecrosis of the femoral head (ONFH) is a refractory disease affecting young adults, resulting in severe hip pain, collapse, and disabling dysfunction. By far, underlying mechanism its pathology unclear, still lack mature effective treatment. Exosomes, regulator cell-cell communication, their cargos may vary response to different physiological or pathological conditions. To date, many studies have demonstrated that exosomes potential become diagnostic marker therapeutic agent human diseases including ONFH. As cell-free agent, are becoming promising tool within this field due crucial role osteogenesis angiogenesis recent decades. Usually, from ONFH tissues could promote damage, while stem cells derived delay repair necrosis. Herein, we describe properties exosomes, discuss effect on pathogenesis, diagnosis, treatment ONFH, examine involvement signaling pathways. We also propose our suggestions for future research hope provide strategy patients with

Language: Английский

Citations

3