Effects of Aging on the Immune and Periosteal Response to Fracture in Mice DOI Open Access
Justin S. King,

Matthew Wan,

Adam Kim

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 6, 2024

Abstract Aging predisposes individuals to reduced bone mass and fragility fractures, which are costly linked high mortality. Understanding how aging affects fracture healing is essential for developing therapies enhance regeneration in older adults. During the inflammatory phase of healing, immune cells recruited injury site as periosteal skeletal stem/progenitor (pSSPCs) rapidly proliferate differentiate into osteochondral lineages, allowing fibrocartilaginous callus formation complete healing. Irrespective age, mesenchymal interact during early incompletely understood, limiting our ability potentially modulate these processes. To address this, we directly analyzed, parallel, at a single-cell level, isolated murine CD45(+) CD45(-) dissected from intact fractured bones, collected three days after injury. Through comprehensive analysis, corroborated by bulk RNA-sequencing, flow cytometry, histology, found decreases pSSPCs proliferative, marked expression genes required an increased senescence signature. We that chemokine Cxcl9 was highly upregulated aged Prrx1+ pSSPCs, predicted with other directly, associated recruitment CD8+ T Cell-to-cell communication analysis provided insight complexity interactions among many cell types regulating impact on Together, results provide age-induced alterations informing development improved therapeutic approaches fractures.

Язык: Английский

Cell communication and relevant signaling pathways in osteogenesis–angiogenesis coupling DOI Creative Commons
LI Shu-qing, Xinjia Cai, Jiahe Guo

и другие.

Bone Research, Год журнала: 2025, Номер 13(1)

Опубликована: Апрель 7, 2025

Язык: Английский

Процитировано

2
Endothelial-mesenchymal crosstalk drives osteogenic differentiation of human osteoblasts through Notch signaling DOI Creative Commons

Perepletchikova Daria,

Polina Kuchur,

Basovich Liubov

и другие.

Cell Communication and Signaling, Год журнала: 2025, Номер 23(1)

Опубликована: Фев. 19, 2025

Angiogenesis and osteogenesis are closely interrelated. The interaction between endothelial bone-forming cells, such as osteoblasts, is crucial for normal bone development repair. Juxtacrine paracrine mechanisms play key roles in cell differentiation towards the osteogenic direction, assuming direct effect of endothelium on differentiation. However, this interplay have yet to be thoroughly studied. Isolated cells (EC) from human umbilical vein osteoblasts (OB) epiphysis femur or tibia were cultured indirect (separated by membrane) contact vitro under conditions. Osteogenic was verified RT-PCR, alizarin red staining. Shotgun proteomics RNA-sequencing used compare both EC OB different co-culture conditions assess EC-OB interplay. To verify role Notch signaling, experiments with modulation performed lentiviral transduction further co-cultivation OB. Additionally, assessed RNA-sequencing. opposite effects depending In contact, enhance differentiation, but cultures, suppress it. Our proteotranscriptomic analysis revealed that osteosuppressive related action factors secreted EC, while osteoinductive properties mediated signaling pathway, which can activated only upon a physical Indeed, co-culture, knockdown Notch1 Notch3 receptors has an inhibitory whereas activation intracellular domain either inductive data indicate dual regulating highlight unique pathway inducing during cell-to-cell interactions. findings study emphasize importance intercellular communication regulation osteoblast maintenance.

Язык: Английский

Процитировано

1
CD47 is required for mesenchymal progenitor proliferation and fracture repair DOI Creative Commons
Robert L. Zondervan, Christina A. Capobianco, Daniel C. Jenkins

и другие.

Bone Research, Год журнала: 2025, Номер 13(1)

Опубликована: Март 3, 2025

Abstract CD47 is a ubiquitous and pleiotropic cell-surface receptor. Disrupting enhances injury repair in various tissues but the role of has not been studied bone injuries. In murine closed-fracture model, CD47-null mice showed decreased callus formation as assessed by microcomputed tomography 10 days post-fracture increased fibrous volume determined histology. To understand cellular basis for this phenotype, mesenchymal progenitors (MSC) were harvested from marrow. MSC large fibroblast colony (CFU-F), significantly less proliferation, fewer cells S-phase, although osteoblast differentiation was unaffected. However, consistent with prior research, endothelial proliferation relative to WT cells. Similarly, ischemic fracture reduced size due reduction 15 days-post fracture. Consistent our vitro results, vivo EdU labeling cell mice, while staining CD31 endomucin demonstrated density. Finally, that administered morpholino, which blocks protein production, phenotype similar fractures suggesting developmental changes knockout mice. Thus, inhibition during healing reduces both non-ischemic healing, part, decreasing proliferation. Furthermore, increase early blood vessel density caused disruption sufficient overcome dysfunction.

Язык: Английский

Процитировано

1
Effects of aging on the immune and periosteal response to fracture injury DOI
Justin S. King,

Matthew Wan,

Adam Kim

и другие.

Bone, Год журнала: 2025, Номер 198, С. 117524 - 117524

Опубликована: Май 15, 2025

Язык: Английский

Процитировано

0
Adipose-derived stem cell exosomal miR-21-5p enhances angiogenesis in endothelial progenitor cells to promote bone repair via the NOTCH1/DLL4/VEGFA signaling pathway DOI Creative Commons
Le Cao, Kai Sun,

Ran Zeng

и другие.

Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Ноя. 8, 2024

Angiogenesis is essential for repairing critical-sized bone defects. Although adipose-derived stem cell (ADSC)-derived exosomes have been shown to enhance the angiogenesis of endothelial progenitor cells (EPCs), underlying mechanisms remain unclear. This study aims explore effects and ADSC-derived in enhancing repair by promoting EPC angiogenesis.

Язык: Английский

Процитировано

3
HIF1 activation safeguards cortical bone formation against impaired oxidative phosphorylation DOI Creative Commons
Mohd Parvez Khan, Elena Sabini, Katherine Beigel

и другие.

JCI Insight, Год журнала: 2024, Номер 9(18)

Опубликована: Авг. 1, 2024

Energy metabolism, through pathways such as oxidative phosphorylation (OxPhos) and glycolysis, plays a pivotal role in cellular differentiation function. Our study investigates the impact of OxPhos disruption cortical bone development by deleting mitochondrial transcription factor A (TFAM). TFAM controls regulating genes. The bone, constituting long bones' rigid shell, is sheathed periosteum, connective tissue layer populated with skeletal progenitors that spawn osteoblasts, bone-forming cells. TFAM-deficient mice presented thinner spontaneous midshaft fractures, compromised periosteal cell bioenergetics, characterized reduced ATP levels. Additionally, they exhibited an enlarged progenitor pool impaired osteoblast differentiation. Increasing hypoxia-inducible 1a (HIF1) activity within cells substantially mitigated detrimental effects induced deletion. HIF1 known to promote glycolysis all types. findings underscore indispensability for proper accrual mass indicate compensatory mechanism between opens new avenues understanding relationship energy metabolism health suggests modulating bioenergetic may provide therapeutic avenue conditions fragility.

Язык: Английский

Процитировано

0
Effects of Aging on the Immune and Periosteal Response to Fracture in Mice DOI Open Access
Justin S. King,

Matthew Wan,

Adam Kim

и другие.

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 6, 2024

Abstract Aging predisposes individuals to reduced bone mass and fragility fractures, which are costly linked high mortality. Understanding how aging affects fracture healing is essential for developing therapies enhance regeneration in older adults. During the inflammatory phase of healing, immune cells recruited injury site as periosteal skeletal stem/progenitor (pSSPCs) rapidly proliferate differentiate into osteochondral lineages, allowing fibrocartilaginous callus formation complete healing. Irrespective age, mesenchymal interact during early incompletely understood, limiting our ability potentially modulate these processes. To address this, we directly analyzed, parallel, at a single-cell level, isolated murine CD45(+) CD45(-) dissected from intact fractured bones, collected three days after injury. Through comprehensive analysis, corroborated by bulk RNA-sequencing, flow cytometry, histology, found decreases pSSPCs proliferative, marked expression genes required an increased senescence signature. We that chemokine Cxcl9 was highly upregulated aged Prrx1+ pSSPCs, predicted with other directly, associated recruitment CD8+ T Cell-to-cell communication analysis provided insight complexity interactions among many cell types regulating impact on Together, results provide age-induced alterations informing development improved therapeutic approaches fractures.

Язык: Английский

Процитировано

0