Multinucleation resets human macrophages for specialized functions at the expense of their identity DOI Creative Commons
Kourosh Ahmadzadeh, Marie Pereira,

Margot Vanoppen

et al.

EMBO Reports, Journal Year: 2023, Volume and Issue: 24(3)

Published: Jan. 4, 2023

Abstract Macrophages undergo plasma membrane fusion and cell multinucleation to form multinucleated giant cells (MGCs) such as osteoclasts in bone, Langhans (LGCs) part of granulomas or foreign‐body (FBGCs) reaction exogenous material. How per se contributes functional specialization mature mononuclear macrophages remains poorly understood humans. Here, we integrate comparative transcriptomics with assays purified human osteoclasts, LGCs FBGCs. Strikingly, all three types MGCs, causes a pronounced downregulation macrophage identity. We show enhanced lysosome‐mediated intracellular iron homeostasis promoting MGC formation. The transition from multinuclear state is accompanied by specific each polykaryon. Enhanced phagocytic mitochondrial function associate FBGCs respectively. Moreover, preferentially express B7‐H3 (CD276) can granuloma‐like clusters vitro , suggesting that their potentiates T activation. These findings demonstrate how cell–cell reset identity an advanced maturation step confers MGC‐specific functionality.

Language: Английский

Mechanisms controlling cellular and systemic iron homeostasis DOI
Bruno Galy, Marcus Conrad, Martina U. Muckenthaler

et al.

Nature Reviews Molecular Cell Biology, Journal Year: 2023, Volume and Issue: 25(2), P. 133 - 155

Published: Oct. 2, 2023

Language: Английский

Citations

306

Fighting age-related orthopedic diseases: focusing on ferroptosis DOI Creative Commons
Qin Ru, Yusheng Li, Wenqing Xie

et al.

Bone Research, Journal Year: 2023, Volume and Issue: 11(1)

Published: March 1, 2023

Abstract Ferroptosis, a unique type of cell death, is characterized by iron-dependent accumulation and lipid peroxidation. It closely related to multiple biological processes, including iron metabolism, polyunsaturated fatty acid the biosynthesis compounds with antioxidant activities, glutathione. In past 10 years, increasing evidence has indicated potentially strong relationship between ferroptosis onset progression age-related orthopedic diseases, such as osteoporosis osteoarthritis. Therefore, in-depth knowledge regulatory mechanisms in diseases may help improve disease treatment prevention. This review provides an overview recent research on its influences bone cartilage homeostasis. begins brief systemic metabolism ferroptosis, particularly potential ferroptosis. presents discussion role promotion loss degradation inhibition osteogenesis. Finally, it focuses future targeting treat intention inspiring further clinical development therapeutic strategies.

Language: Английский

Citations

100

Mitochondrial Dysfunction in Periodontitis and Associated Systemic Diseases: Implications for Pathomechanisms and Therapeutic Strategies DOI Open Access
Yifei Deng,

Junhong Xiao,

Li Ma

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(2), P. 1024 - 1024

Published: Jan. 13, 2024

Periodontitis is a chronic infectious disorder damaging periodontal tissues, including the gingiva, ligament, cementum, and alveolar bone. It arises from complex interplay between pathogenic oral bacteria host immune response. Contrary to previous view of “energy factories”, mitochondria have recently been recognized as semi-autonomous organelles that fine-tune cell survival, death, metabolism, other functions. Under physiological conditions, tissue cells participate in dynamic processes, differentiation, mineralization, regeneration. These fundamental activities depend on properly functioning mitochondria, which play crucial role through bioenergetics, dynamics, mitophagy, quality control. However, during initiation progression periodontitis, mitochondrial control compromised due range challenges, such bacterial–host interactions, inflammation, oxidative stress. Currently, mounting evidence suggests dysfunction serves common pathological mechanism linking periodontitis with systemic conditions like type II diabetes, obesity, cardiovascular diseases. Therefore, targeting intervene multiple associated diseases holds great therapeutic potential. This review provides advanced insights into Moreover, we emphasize significance diverse modulators signaling pathways regulate function cells.

Language: Английский

Citations

29

Regulating Type H Vessel Formation and Bone Metabolism via Bone‐Targeting Oral Micro/Nano‐Hydrogel Microspheres to Prevent Bone Loss DOI Creative Commons
Junjie Li, Gang Wei,

Gongwen Liu

et al.

Advanced Science, Journal Year: 2023, Volume and Issue: 10(15)

Published: March 26, 2023

Abstract Postmenopausal osteoporosis is one of the most prevalent skeletal disorders in women and featured by imbalance between intraosseous vascularization bone metabolism. In this study, a pH‐responsive shell–core structured micro/nano‐hydrogel microspheres loaded with polyhedral oligomeric silsesquioxane (POSS) using gas microfluidics ionic cross‐linking technology are developed. This microsphere system (PDAP@Alg/Cs) can achieve oral delivery, intragastric protection, intestinal slow/controlled release, active targeting to tissue, thus negatively affecting angiogenesis osteoclastogenesis. According biodistribution data, PDAP@Alg/Cs successfully enhance drug absorption bioavailability through intestine adhesion after administration. vitro vivo experiments reveal that promoted type H vessel formation inhibited resorption, effectively mitigating loss activating HIF‐1 α /VEGF signaling pathway promoting heme oxygenase‐1 (HO‐1) expression. conclusion, novel simultaneously accelerate decrease offering brand‐new approach prevent postmenopausal osteoporosis.

Language: Английский

Citations

43

The Role of Trace Elements and Minerals in Osteoporosis: A Review of Epidemiological and Laboratory Findings DOI Creative Commons
Anatoly V. Skalny, Michael Aschner, Ekaterina Silina

et al.

Biomolecules, Journal Year: 2023, Volume and Issue: 13(6), P. 1006 - 1006

Published: June 17, 2023

The objective of the present study was to review recent epidemiological and clinical data on association between selected minerals trace elements osteoporosis, as well discuss molecular mechanisms underlying these associations. We have performed a search in PubMed-Medline Google Scholar databases using MeSH terms "osteoporosis", "osteogenesis", "osteoblast", "osteoclast", "osteocyte" with names particular through 21 March 2023. demonstrate that physiological nutritional levels promote osteogenic differentiation up-regulation BMP-2 Wnt/β-catenin signaling, other pathways. miRNA epigenetic effects were also involved regulation minerals. antiresorptive effect associated inhibition osteoclastogenesis. At same time, bone health appeared be dose-dependent low doses promoting an effect, whereas high exerted opposite which promoted resorption impaired formation. Concomitant results laboratory studies, several trials studies demonstrated supplementation Zn, Mg, F, Sr may improve quality, thus inducing antiosteoporotic effects.

Language: Английский

Citations

26

NRF2 is essential for iron-overload stimulated osteoclast differentiation through regulation of redox and iron homeostasis DOI
Jian Zhang, Lingyan Zhang, Gang Yao

et al.

Cell Biology and Toxicology, Journal Year: 2023, Volume and Issue: 39(6), P. 3305 - 3321

Published: Oct. 19, 2023

Language: Английский

Citations

23

The Manganese–Bone Connection: Investigating the Role of Manganese in Bone Health DOI Open Access
Gulaim Taskozhina, Gulnara Batyrova, Gulmira Umarova

et al.

Journal of Clinical Medicine, Journal Year: 2024, Volume and Issue: 13(16), P. 4679 - 4679

Published: Aug. 9, 2024

The complex relationship between trace elements and skeletal health has received increasing attention in the scientific community. Among these minerals, manganese (Mn) emerged as a key element affecting bone metabolism integrity. This review examines multifaceted role of Mn health, including its effects on regeneration, mineralization, overall strength. article is based synthesis experimental models, epidemiologic studies, clinical trials mechanisms effect metabolism. Current research data show that actively involved processes remodeling by modulating activity osteoblasts osteoclasts, well main cells regulate formation resorption. ions have profound mineralization density intricately regulating signaling pathways enzymatic reactions cells. Additionally, superoxide dismutase (MnSOD), located mitochondria, plays crucial osteoclast differentiation function, protecting osteoclasts from oxidative damage. Understanding nuances Mn’s interaction with essential for optimizing strategies, potentially preventing managing diseases. Key findings include stimulation osteoblast proliferation differentiation, inhibition osteoclastogenesis, preservation mass through RANK/RANKL/OPG pathway. These results underscore importance maintaining highlight need further into therapeutic potential.

Language: Английский

Citations

10

From death to birth: how osteocyte death promotes osteoclast formation DOI Creative Commons
Weijie Zhao, Jiale Qian, Ji Li

et al.

Frontiers in Immunology, Journal Year: 2025, Volume and Issue: 16

Published: March 17, 2025

Bone remodeling is a dynamic and continuous process involving three components: bone formation mediated by osteoblasts, resorption osteoclasts, formation-resorption balancing regulated osteocytes. Excessive osteocyte death found in various diseases, such as postmenopausal osteoporosis (PMOP), osteoclasts are increased activated at sites. Currently, apart from apoptosis necrosis previously established, more forms of cell reported, including necroptosis, ferroptosis pyroptosis. These play important role the development inflammatory diseases diseases. Increasing studies have revealed that promote osteoclast via different mechanism, actively secreting pro-inflammatory pro-osteoclastogenic cytokines, tumor factor alpha (TNF-α) receptor activator nuclear factor-kappa B ligand (RANKL), or passively releasing damage associated molecule patterns (DAMPs), high mobility group box 1 (HMGB1). This review summarizes established potential mechanisms which regulate formation, aiming to provide better understanding disease therapeutic target.

Language: Английский

Citations

1

Redox signaling and antioxidant defense in osteoclasts DOI

Huaqiang Tao,

Xuefeng Li,

Qiufei Wang

et al.

Free Radical Biology and Medicine, Journal Year: 2024, Volume and Issue: 212, P. 403 - 414

Published: Jan. 1, 2024

Language: Английский

Citations

8

The role and mechanism of RNA-binding proteins in bone metabolism and osteoporosis DOI

Jiaqiang Wu,

Liyan Niu,

Kangping Yang

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: 96, P. 102234 - 102234

Published: Feb. 16, 2024

Language: Английский

Citations

7