Rabbit bone tissue sample sequencing
Ontology highlight
ABSTRACT:
PROVIDER: PRJEB86792 | ENA |
REPOSITORIES: ENA
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Project description:<p>Chronic, drug-resistant bone infection caused by methicillin-resistant Staphylococcus aureus (MRSA) features an immunosuppressive niche enabling persistent infection and impaired bone healing. Specific treatment requires initial antibacterial immune activation against infection, followed by reshaping an anti-inflammatory microenvironment for later bone repair. Here, we screen out Lactococcus lactis outer membrane vesicles (Lac-OMVs) with first-stage dendritic cells (DCs) activation and later-stage inflammatory macrophage repolarization potential. Mechanistically, enrichment of the nicotinamide metabolism pathway within Lac-OMVs is discovered, with nicotinamide adenine dinucleotide (NAD+) as a key anti-inflammatory mediator. NAD+-enriched Lac-OMVs (NAD+-Lac-OMVs) is thus metabolically engineered via targeted culture condition optimizing, exerting biphasic immunomodulatory effects: (i) Early-stage DCs activation establishes robust humoral immunity, protecting against primary and recurrent MRSA challenge (99.35 % and 98.07 % bacteria clearance each); (ii) Later-stage targeted NAD+ delivery reprograms inflammatory macrophages at defect site, resolving inflammation and establishing a pro-osteogenic microenvironment (~10 times higher bone-repair rate).</p>
2026-03-19 | MTBLS14091 | MetaboLights
Project description:Bone diseases profoundly affect patients, particularly the elderly, leading to severe health complications and disabilities. Osteoblasts play a crucial role in bone formation and are ideal candidates for treating bone diseases and engineering living materials. However, the stem and progenitor cells that give rise to osteoblasts, as well as osteoblasts themselves, exhibit dysfunction with aging. Although chemical reprogramming of fibroblasts into osteoblasts has been achieved, effective cell-based therapies or living materials have not been established in clinical practice. Here, we present a method using small molecules to achieve complete osteoblastic specification from human fibroblasts across all age groups. By targeting Wnt signaling pathways and modularizing small molecules and their combinations based on their effects on stage-specific genes, we optimized the temporal regulation of small molecules in reprogramming, achieving healthy induced osteoblasts(iOBs). The iOBs with traits of young native osteoblasts are ideal for forming transplantable tissue spheroids with improved survival, self-bone formation, and accelerated local angiogenesis in vivo, promoting effective bone defect repair. The material-free spheroids function as living, self-scaffolding building blocks for biofunctional constructs that reproduce tissue composition, maintain high cell density, and support matrix remodeling, offering a promising avenue for clinical autologous bone defect repair.
2025-05-07 | GSE278615 | GEO
Project description:Bone diseases profoundly affect patients, particularly the elderly, leading to severe health complications and disabilities. Osteoblasts play a crucial role in bone formation and are ideal candidates for treating bone diseases and engineering living materials. However, the stem and progenitor cells that give rise to osteoblasts, as well as osteoblasts themselves, exhibit dysfunction with aging. Although chemical reprogramming of fibroblasts into osteoblasts has been achieved, effective cell-based therapies or living materials have not been established in clinical practice. Here, we present a method using small molecules to achieve complete osteoblastic specification from human fibroblasts across all age groups. By targeting Wnt signaling pathways and modularizing small molecules and their combinations based on their effects on stage-specific genes, we optimized the temporal regulation of small molecules in reprogramming, achieving healthy induced osteoblasts(iOBs). The iOBs with traits of young native osteoblasts are ideal for forming transplantable tissue spheroids with improved survival, self-bone formation, and accelerated local angiogenesis in vivo, promoting effective bone defect repair. The material-free spheroids function as living, self-scaffolding building blocks for biofunctional constructs that reproduce tissue composition, maintain high cell density, and support matrix remodeling, offering a promising avenue for clinical autologous bone defect repair.
2025-05-07 | GSE278288 | GEO
Project description:Understanding the dynamic changes of cells during calvarial bone repair is crucial for identifying novel therapeutic targets to enhance bone regeneration. However, the cellular changes and intercellular communication during calvarial defect repair remain poorly understood. To address this, we performed single-cell RNA sequencing on tissues collected at different time points post-defect. Our analysis revealed a significant enhancement in intercellular communication following defect, particularly among stem cells, endothelial cells, pericytes, and macrophages. Pathways related to neurogenesis were significantly enriched after defect. Furthermore, we found that inhibiting sympathetic nerves promoted calvarial bone repair. Mechanistically, sympathetic nerve inhibition enhanced angiogenesis and osteogenesis by promoting interactions between pericytes and endothelial cells, generating a novel senescenced Arg1+ macrophages, which contributed to bone repair by secreting osteogenesis-related cytokines. Besides, inhibition of sympathetic nerves promotes the generation of Shisa3+ suture cell subpopulation and enhances osteogenic differentiation capacity. Importantly, senolytics abrogated the repair benefits brought about by sympathetic nerve inhibition, underscoring the critical role of senescent macrophages in the repair process.
2025-12-31 | GSE298251 | GEO
Project description:The neuroregulatory effects of sensory nerves in bone repair have recently begun to be elucidated, principally through loss of function studies. However, the potential therapeutic efficacy of boosting nerve-to-bone interactions, as well as the elucidation of downstream signaling pathways remains poorly studied. Here, two parallel approaches were utilized to enhance sensory nerve-to-bone interactions using a mouse calvarial bone defect model system. Pharmacologic activation of TrkA with gambogic amide induced bone-associated nerve ingrowth and markedly improved calvarial bone healing. Single-cell RNA sequencing analysis of cells derived from the defect site revealed shifts in cluster proportions, with enrichment of immune cell populations in TrkA agonist-treated mice. Within the skeletal cell lineage, TrkA agonism enhanced osteoblast differentiation while suppressing fibroblastic differentiation. Pathway analysis showed increased activity of Hedgehog, Wnt, BMP, and other osteogenic pathways. Further investigation of intercellular communication identified elevated Hedgehog signaling pathway specifically from DRG neurons. In summary, activation of TrkA-positive sensory nerves stimulates hedgehog pathway activity in local mesenchymal stem and progenitor cells, promoting osteoblast differentiation and bone formation. Our study thus elucidates signaling mechanisms underlying neurogenically-enhanced bone repair.
2026-02-05 | GSE266598 | GEO
Project description:Engineering Fibroblast with Reprogramming and Spheronization for Bone Defect Repair
| PRJNA1166210 | ENA
Project description:Engineering Fibroblast with Reprogramming and Spheronization for Bone Defect Repair
| PRJNA1168097 | ENA
Project description:Bone defect repair remains a major clinical challenge. This study presents a novel strategy using a 3D-printed piezoelectric hydrogel scaffold—composed of gelatin methacrylate (GelMA), hydroxyapatite (HA), and barium titanate (BTO)—for functional bone tissue engineering. The GelMA/HA/BTO (GelHABT) scaffold exhibited a well-defined porous structure, enhanced mechanical stability, and, crucially, reliable piezoelectric responsiveness. This key feature enables the material to convert external mechanical stimuli, such as low-intensity pulsed ultrasound (LIPUS), into endogenous electrical signals. In vitro, the scaffold promoted BMSCs adhesion, proliferation, and osteogenic differentiation, with performance significantly enhanced under LIPUS stimulation. Mechanistic insights revealed that the piezoelectric microenvironment remodeled the cellular miRNA expression profile, particularly up-regulating osteogenesis-related miR-29b-3p and activating the AMPK signaling pathway. Collectively, this ultrasound-responsive, gene-regulating scaffold represents a promising approach for treating bone defects by leveraging piezoelectricity to actively stimulate bone regeneration.
2026-01-28 | GSE317440 | GEO
Project description:The vascular wall from diverse human organs is a source of mesenchymal progenitor cells. FACS purified human perivascular stem cells (PSC), identified by expression of CD146 or CD34, were observed to induce mitogenic, pro-migratory, and pro-osteogenic effects on osteoprogenitor cells via elaboration of extracellular vesicles (EV). These EV mediated effects were dependent on surface-associated tetraspanin expression, including CD9 and CD81. PSC derived EV stimulate bone defect repair, and do so via stimulation of skeletal progenitor cell proliferation, migration, and osteodifferentiation. In sum, PSC-EV represent an ‘off the shelf’ alternative for bone tissue engineering and regenerative medicine.
2019-10-08 | GSE118961 | GEO