Malatl fine-tunes bone homeostasis by orchestrating cellular crosstalk and the β-catenin-OPG/Jagged1 pathway DOI Creative Commons
Yongli Qin,

Jumpei Shirakawa,

Cheng Xu

и другие.

eLife, Год журнала: 2024, Номер 13

Опубликована: Июль 1, 2024

The IncRNA Malat1 was initially believed to be dispensable for physiology due the lack of observable phenotypes in knockout (KO) mice. However, our study challenges this conclusion. We found that both KO and conditional mice osteoblast lineage exhibit significant osteoporosis. Mechanistically, acts as an intrinsic regulator osteoblasts promote osteogenesis. Interestingly, does not directly affect osteoclastogenesis but inhibits a non-autonomous manner vivo via integrating crosstalk between multiple cell types, including osteoblasts, osteoclasts, chondrocytes. Our findings substantiate existence novel remodeling network which serves central by binding β-catenin functioning through β-catenin-OPG/Jagged1 pathway In pathological conditions, significantly promotes bone regeneration fracture healing. Bone homeostasis are crucial well-being. discoveries establish previous unrecognized paradigm model function skeletal system, providing mechanistic insights into how lncRNA integrates cellular molecular networks fine tune tissue homeostasis, repair.

Язык: Английский

Csf1 from marrow adipogenic precursors is required for osteoclast formation and hematopoiesis in bone DOI Creative Commons
Leilei Zhong, Jiawei Lu,

Jiankang Fang

и другие.

eLife, Год журнала: 2023, Номер 12

Опубликована: Фев. 13, 2023

Colony-stimulating factor 1 (Csf1) is an essential growth for osteoclast progenitors and important regulator bone resorption. It remains elusive which mesenchymal cells synthesize Csf1 to stimulate osteoclastogenesis. We recently identified a novel cell population, marrow adipogenic lineage precursors (MALPs), in bone. Compared other subpopulations, MALPs expressed at much higher level this expression was further increased during aging. To investigate its role, we constructed MALP-deficient CKO mice using Adipoq Cre . These had femoral trabecular mass, but their cortical appeared normal. In comparison, depletion of the entire Prrx1 led more striking high mass phenotype, suggesting that additional subpopulations secrete Csf1. TRAP staining revealed diminished osteoclasts secondary spongiosa region mice, not chondral-osseous junction nor endosteal surface Moreover, were resistant LPS-induced calvarial osteolysis. Bone cellularity, hematopoietic progenitors, macrophages also reduced these mice. Taken together, our studies demonstrate control remodeling hematopoiesis.

Язык: Английский

Процитировано

31
Skeletal stem and progenitor cells in bone development and repair DOI Creative Commons
Dana Trompet, Seppe Melis, Andrei S. Chagin

и другие.

Journal of Bone and Mineral Research, Год журнала: 2024, Номер unknown

Опубликована: Апрель 30, 2024

Abstract Bone development, growth, and repair are complex processes involving various cell types interactions, with central roles played by skeletal stem progenitor cells. Recent research brought new insights into the precursor populations that mediate intramembranous endochondral bone development. Later in life, many of cellular molecular mechanisms determining development reactivated upon fracture, powerful trauma-induced signaling cues triggering a variety postnatal stem/progenitor cells (SSPCs) residing near defect. Interestingly, this injury context, current evidence suggests fates both SSPCs differentiated can be considerably flexible dynamic, multiple sources activated to operate as functional progenitors generating chondrocytes and/or osteoblasts. The combined implementation vivo lineage tracing, surface marker-based selection, single-cell analyses, high-resolution situ imaging has strongly improved our diversity developmental reparative subsets, while also unveiling complexity their dynamics, hierarchies, relationships. Albeit incompletely understood at present, findings supporting flexibility possibly plasticity among osteogenic challenge classical dogma single primitive, self-renewing, multipotent driving tissue formation regeneration from apex hierarchical strictly unidirectional differentiation tree. We here review state field newest discoveries origin, identity, during discuss contributions adult SSPC fracture repair, reflect on dynamism relationships precursors lineages. Further directed unraveling heterogeneity capacities SSPCs, well regulatory fate functioning, will offer vital options for clinical translation toward compromised healing regenerative medicine.

Язык: Английский

Процитировано

12
Osteoimmunology of Fracture Healing DOI Creative Commons

Kristin Happ Molitoris,

Mingjian Huang, Gurpreet S. Baht

и другие.

Current Osteoporosis Reports, Год журнала: 2024, Номер 22(3), С. 330 - 339

Опубликована: Апрель 15, 2024

The purpose of this review is to summarize what known in the literature about role inflammation plays during bone fracture healing. Bone healing progresses through four distinct yet overlapping phases: formation hematoma, development cartilaginous callus, bony and finally remodeling callus. Throughout process, a critical robust

Язык: Английский

Процитировано

10
Skeletal stem and progenitor cells in bone physiology, ageing and disease DOI
Seppe Melis, Dana Trompet, Andrei S. Chagin

и другие.

Nature Reviews Endocrinology, Год журнала: 2024, Номер unknown

Опубликована: Окт. 8, 2024

Язык: Английский

Процитировано

7
miR-208a-3p discriminates osteoporosis, predicts fracture, and regulates osteoclast activation through targeting STC1 DOI Creative Commons
Haohua Qian, Fei Jia,

Huiling Qin

и другие.

Journal of Orthopaedic Surgery and Research, Год журнала: 2025, Номер 20(1)

Опубликована: Янв. 27, 2025

Osteoporosis (OP) frequently occurs in post-menopausal women, increasing the risk of fracture. Early screening OP could improve prevention fractures.This study focused on significance miR-208a-3p diagnosing and development regulation, aiming to explore a novel biomarker therapeutic target for OP. The enrolled total 154 women grouping was performed based incidence evaluated from perspectives menopausal correlation, diagnosis, fracture prediction. In mechanism, regulatory effect mechanism osteoclast activation investigated. menopause-related showing negative correlation with E2 positive correlations FSH LH. Significant upregulation observed showed significant diagnostic potential. Increasing positively correlated bone metabolism markers negatively BMD Moreover, also identified as factor STC1 direct regulated by miR-208a-3p. Silencing significantly alleviated macrophage inflammation osteoblast activation, which reversed knockdown STC1. Serum served women. further mediated via targeting

Язык: Английский

Процитировано

1
Adipocyte- and Monocyte-Mediated Vicious Circle of Inflammation and Obesity (Review of Cellular and Molecular Mechanisms) DOI Open Access
Н. М. Тодосенко, О. Г. Хазиахматова, В. В. Малащенко

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(15), С. 12259 - 12259

Опубликована: Июль 31, 2023

Monocytes play a key role in the development of metabolic syndrome, and especially obesity. Given complex features their from progenitor cells, whose regulation is mediated by interactions with bone marrow adipocytes, importance detailed study heterogeneous composition monocytes at molecular systemic levels becomes clear. Research argues for as indicators changes body’s metabolism possibility developing therapeutic strategies to combat obesity components syndrome based on manipulations monocyte compound immune response. An in-depth heterogeneity bone-marrow-derived adipocytes could provide answers many questions about pathogenesis reveal potential.

Язык: Английский

Процитировано

16
Targeting bone homeostasis regulation: potential of traditional Chinese medicine flavonoids in the treatment of osteoporosis DOI Creative Commons

Jiazhe Du,

Yincang Wang,

Chengliang Wu

и другие.

Frontiers in Pharmacology, Год журнала: 2024, Номер 15

Опубликована: Апрель 2, 2024

Osteoporosis is a systemic metabolic disease characterized by disrupted bone formation/resorption and homeostasis. Flavonoids extracted from traditional Chinese medicinal plants regulate homeostasis intervening in differentiating marrow mesenchymal stem cells, balancing the immune system, inhibiting oxidative stress response, reversing iron overload. The target molecules signaling pathways, such as Wnt/β-catenin OPG/RANKL/RANK, directly affect osteoblast/osteoclast activity, exhibiting significant potential treatment of OP. Therefore, this study presents systematic review recent literature to provide comprehensive information on medicine flavonoids involved regulation Also, molecular mechanisms pharmacological uses these metabolites are summarized, their clinical translation development discussed.

Язык: Английский

Процитировано

5
Obesity Limits Utility of Vertebral Bone Quality Score for Opportunistic Osteopenia/Osteoporosis Screening in Cervical Surgery Patients DOI Creative Commons

Mingliang Shi,

Cheng Ye,

Baocheng Niu

и другие.

Global Spine Journal, Год журнала: 2025, Номер unknown

Опубликована: Март 1, 2025

Comparative study. The vertebral bone quality (VBQ) score is a validated opportunistic screening tool for mineral density (BMD). Obesity, often associated with hyperlipidemia and fat infiltration, may result in lower VBQ-derived BMD. However, studies have shown that dual-energy x-ray absorptiometry (DXA)-derived BMD tends to increase obesity. Given this paradox, the aim of study was evaluate effect obesity on utility VBQ osteopenia/osteoporosis screening. A total 310 consecutive patients degenerative cervical myelopathy were included. Body mass index (BMI) classified into underweight/normal, overweight, groups. Pearson's correlation assessed associations BMI score, Hounsfield unit (HU) values, T-score. HU values discriminate normal from analyzed using receiver operating characteristic curve analysis area under (AUC). higher T-score, but not values. between T-score decreased increasing BMI, eventually becoming nonsignificant group (r = 0.241, P .082). effective identifying obese (AUC 0.59, .282). Compared several subgroups 0.75 0.88, < .001). Cervical no longer reliable indicator DXA-derived patients. Even when appears normal, it should be solely relied upon preclude further DXA evaluation.

Язык: Английский

Процитировано

0
Marrow adipogenic lineage precursors (MALPs) facilitate bone marrow recovery after chemotherapy DOI Creative Commons
Huan Wang, Lutian Yao, Leilei Zhong

и другие.

Bone, Год журнала: 2025, Номер unknown, С. 117446 - 117446

Опубликована: Март 1, 2025

Язык: Английский

Процитировано

0
Combination treatment with anti-RANKL and antibiotics for preventing joint destruction in septic arthritis DOI
Zhicheng Hu, Meghshree Deshmukh, Anders Jarneborn

и другие.

JCI Insight, Год журнала: 2025, Номер 10(6)

Опубликована: Март 11, 2025

Septic arthritis, the most severe joint disease, is frequently caused by Staphylococcus aureus (S. aureus). A substantial proportion of patients with septic arthritis experience poor outcomes, often necessitating replacement surgery. Here, we show that monocyte depletion confers full protection against bone erosion in a mouse model. In infected synovium, Ly6Chi monocytes exhibited increased expression osteoclastogenesis-related molecules, including CCR2, c-Fms, and RANK. S. lipoproteins induced elevated levels RANKL, MCSF, CCL2 joints, synovial fibroblasts identified as major RANKL producer. Anti-RANKL treatment prevented destruction both local hematogenous murine models. Importantly, combining anti-RANKL antibiotics provided robust damage. Our results indicate infiltration transformation into bone-destructive, osteoclast-like cells are key mechanisms arthritis. Combining antibiotic therapy represents promising this devastating disease.

Язык: Английский

Процитировано

0