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Project description:The periosteum contains a highly osteogenic and neuro-vascular microenvironment that is essential for cortical bone formation and regeneration. Resident tissue macrophages (RTMs) are critical for maintaining tissue-specific niches and participating in tissue regeneration. However, the characteristics, origin and functions of periosteum-resident macrophages (PRMs) remain largely unknown. In this study, we demonstrated that PRMs are generated during embryonic hematopoiesis and are self-maintained locally during regeneration. Furthermore, by single-cell RNA sequencing analysis of periosteum myeloid cells, CX3CR1+CD45+ACE+ and CX3CR1+CD45+CD74+ cells were identified as vascular-associated and neuro-associated PRMs, respectively. Both cell types were found to arise from CX3CR1+CD168+CD45+ PRMs and shown to play critical roles in maintaining the periosteum neuro-vascular niche and promoting early-stage cortical bone regeneration. Importantly, the neuro-vascular characteristic of PRMs are directly modulated via Periostin, the essential ECM distributed in periosteum. These findings elucidate the characteristics and origins of PRMs and reveal their essential roles in maintaining the local niche and cortical bone regeneration as well as highlighting the potential value of PRMs as a therapeutic target in bone regeneration.
2024-06-01 | GSE190483 | GEO
Project description:The periosteum contains a highly osteogenic and neuro-vascular microenvironment that is essential for cortical bone formation and regeneration. Resident tissue macrophages (RTMs) are critical for maintaining tissue-specific niches and participating in tissue regeneration. However, the characteristics, origin and functions of periosteum-resident macrophages (PRMs) remain largely unknown. In this study, we demonstrated that PRMs are generated during embryonic hematopoiesis and are self-maintained locally during regeneration. Furthermore, by single-cell RNA sequencing analysis of periosteum myeloid cells, CX3CR1+CD45+ACE+ and CX3CR1+CD45+CD74+ cells were identified as vascular-associated and neuro-associated PRMs, respectively. Both cell types were found to arise from CX3CR1+CD168+CD45+ PRMs and shown to play critical roles in maintaining the periosteum neuro-vascular niche and promoting early-stage cortical bone regeneration. Importantly, the neuro-vascular characteristic of PRMs are directly modulated via Periostin, the essential ECM distributed in periosteum. These findings elucidate the characteristics and origins of PRMs and reveal their essential roles in maintaining the local niche and cortical bone regeneration as well as highlighting the potential value of PRMs as a therapeutic target in bone regeneration.
2024-06-01 | GSE190478 | GEO
Project description:The periosteum contains a highly osteogenic and neuro-vascular microenvironment that is essential for cortical bone formation and regeneration. Resident tissue macrophages (RTMs) are critical for maintaining tissue-specific niches and participating in tissue regeneration. However, the characteristics, origin and functions of periosteum-resident macrophages (PRMs) remain largely unknown. In this study, we demonstrated that PRMs are generated during embryonic hematopoiesis and are self-maintained locally during regeneration. Furthermore, by single-cell RNA sequencing analysis of periosteum myeloid cells, CX3CR1+CD45+ACE+ and CX3CR1+CD45+CD74+ cells were identified as vascular-associated and neuro-associated PRMs, respectively. Both cell types were found to arise from CX3CR1+CD168+CD45+ PRMs and shown to play critical roles in maintaining the periosteum neuro-vascular niche and promoting early-stage cortical bone regeneration. Importantly, the neuro-vascular characteristic of PRMs are directly modulated via Periostin, the essential ECM distributed in periosteum. These findings elucidate the characteristics and origins of PRMs and reveal their essential roles in maintaining the local niche and cortical bone regeneration as well as highlighting the potential value of PRMs as a therapeutic target in bone regeneration.
2024-06-01 | GSE190476 | GEO
Project description:Periosteal stem cells are critical for bone regeneration, while the numbers will decrease with age. This study focused on whether Prx1+ cell, a kind of periosteal stem cell, could stimulate bone regeneration in aged mice. Four weeks and 12 months old Prx1CreER-GFP; Rosa26tdTomato mice were used to reveal the degree of Prx1+ cells participating in the femoral fracture healing procedure. One week, 8 weeks, 12 and 24 months old Prx1CreER-GFP mice were used to analyse the real-time distribution of Prx1+ cells. Twelve months old C57BL/6 male mice (n = 96) were used to create the bone defect model and, respectively, received hydrogel, hydrogel with Prx1- mesenchymal stem cells and hydrogel with Prx1+ cells. H&E staining, Synchrotron radiation-microcomputed tomography and mechanical test were used to analyse the healing results. The results showed that tdTomato+ cells were involved in bone regeneration, especially in young mice. At the same time, GFP+ cells decreased significantly with age. The Prx1+ cells group could significantly improve bone regeneration in the murine bone defect model via directly differentiating into osteoblasts and had better osteogenic differentiation ability than Prx1- mesenchymal stem cells. Our finding revealed that the quantity of Prx1+ cells might account for decreased bone regeneration ability in aged mice, and transplantation of Prx1+ cells could improve bone regeneration at the bone defect site.
| S-EPMC7579685 | biostudies-literature
Project description:The periosteum, a highly vascularized thin tissue, has excellent osteogenic and bone regenerative abilities. The generation of periosteum-mimicking tissue has become a novel strategy for bone defect repair and regeneration, especially in critical-sized bone defects caused by trauma and bone tumor resection. Here, we utilized a bone morphogenetic protein-2 (BMP-2)-loaded scaffold to create periosteum-like tissue (PT) in vivo, mimicking the mesenchymal condensation during native long bone development. We found that BMP-2-induced endochondral ossification plays an indispensable role in the construction of PTs. Moreover, we confirmed that BMP-2-induced PTs exhibit a similar architecture to the periosteum and harbor abundant functional periosteum-like tissue-derived cells (PTDCs), blood vessels, and osteochondral progenitor cells. Interestingly, we found that the addition of chondroitin sulfate (CS), an essential component of the extracellular matrix (ECM), could further increase the abundance and enhance the function of recruited PTDCs from the PTs and finally increase the regenerative capacity of the PTs in autologous transplantation assays, even in old mice. This novel biomimetic strategy for generating PT through in vivo endochondral ossification deserves further clinical translation.
| S-EPMC8720863 | biostudies-literature
Project description:Spontaneous bone regeneration could occur to reestablish mandibular bony continuity in patients who underwent partial or total mandibulectomy for tumors with periosteum-preserving. However, scarce data is available related to the precise role of periosteum in this bone regeneration. Therefore we aimed to investigate the gene expression of periosteum that were involved in the mandibular bone regeneration. Mandibular segmental defects were created in six mini-pigs with periosteum preserved. The periosteum of defects and control site were harvested at 1 and 2 weeks. Gene ontology (GO) analysis showed that the mechanisms concerning immature wound healing were clearly up-regulated at week 1. In contrast, by week-2, the GO categories of skeletal development, ossification and bone mineralization were significantly over-represented at week-2 with several genes encoding cell differentiation, extracellular matrix formation, and anatomical structure development. Furthermore, Tgfβ/Bmp, Wnt and Notch signaling were all related to the osteogenic process in this study. Besides osteogenesis, genes related to angiogenesis and neurogenesis were also prominent at week-2. These findings revealed that the gene expression profile of the periosteum's cells participating in bone regeneration varied in different time points, and numbers of candidate genes that differentially expressed during early healing stages of intramembranous bone regeneration were suggested.
| S-EPMC5648814 | biostudies-literature
Project description:ObjectiveTo investigate the dynamic expression of NFAT family of periosteum in guided bone regeneration process.Material and methodsThe swine ribs on one side were used as the trauma group and the contralateral side as the control group. After rib segment was removed, periosteum was sutured to form a closed cavity mimicking guided bone regeneration. The periosteum and regenerated bone tissue were collected at nine time points for gene sequencing and hematoxylin-eosin staining. The expression data of each member were extracted for analysis. Expression correlations among various members were analyzed.ResultsStaining showed the guided bone regeneration was almost completed 1 month after the operation with later stage for bone remodeling. The expression levels of each member in both groups changed greatly, especially within postoperative 1.5 months. The expression of NFATc1 and NFATC2IP in trauma group was significantly correlated with those of control group. The foldchange of each member also had large fluctuations especially within 1.5 months. In the trauma group, NFATc2 and NFATc4 were significantly upregulated, and there was a significant aggregation correlation of NFAT family expression between the various time points within one month, similar to the "pattern-block" phenomenon.ConclusionThis study revealed the dynamic expression of NFAT family in guided bone regeneration, and provided a reference for the specific mechanism. The first 1.5 months is a critical period and should be paid attention to. The significant high-expression of NFATc2 and NFATc4 may role importantly in this process, which needs further research to verify it.
| S-EPMC9327338 | biostudies-literature
Project description:Autograft is superior to both allograft and synthetic bone graft in repair of large structural bone defect largely due to the presence of multipotent mesenchymal stem cells in periosteum. Recent studies have provided further evidence that activation, expansion and differentiation of the donor periosteal progenitor cells are essential for the initiation of osteogenesis and angiogenesis of donor bone graft healing. The formation of donor cell-derived periosteal callus enables efficient host-dependent graft repair and remodeling at the later stage of healing. Removal of periosteum from bone autograft markedly impairs healing whereas engraftment of multipotent mesenchymal stem cells on bone allograft improves healing and graft incorporation. These studies provide rationale for fabrication of a biomimetic periosteum substitute that could fit bone of any size and shape for enhanced allograft healing and repair. The success of such an approach will depend on further understanding of the molecular signals that control inflammation, cellular recruitment as well as mesenchymal stem cell differentiation and expansion during the early phase of the repair process. It will also depend on multidisciplinary collaborations between biologists, material scientists and bioengineers to address issues of material selection and modification, biological and biomechanical parameters for functional evaluation of bone allograft healing.
| S-EPMC2584255 | biostudies-other
Project description:Ionizing radiation and chemotherapy deplete hematopoietic stem cells and damage the vascular niche wherein hematopoietic stem cells reside. Hematopoietic stem cell regeneration requires signaling from an intact bone marrow (BM) vascular niche, but the mechanisms that control BM vascular niche regeneration are poorly understood. We report that BM vascular endothelial cells secrete semaphorin 3 A (SEMA3A) in response to myeloablation and SEMA3A induces p53 - mediated apoptosis in BM endothelial cells via signaling through its receptor, Neuropilin 1 (NRP1), and activation of cyclin dependent kinase 5. Endothelial cell - specific deletion of Nrp1 or Sema3a or administration of anti-NRP1 antibody suppresses BM endothelial cell apoptosis, accelerates BM vascular regeneration and concordantly drives hematopoietic reconstitution in irradiated mice. In response to NRP1 inhibition, BM endothelial cells increase expression and secretion of the Wnt signal amplifying protein, R spondin 2. Systemic administration of anti - R spondin 2 blocks HSC regeneration and hematopoietic reconstitution which otherwise occurrs in response to NRP1 inhibition. SEMA3A - NRP1 signaling promotes BM vascular regression following myelosuppression and therapeutic blockade of SEMA3A - NRP1 signaling in BM endothelial cells accelerates vascular and hematopoietic regeneration in vivo.
| S-EPMC8635308 | biostudies-literature
Project description:Tissue-resident macrophages in white adipose tissue (WAT) dynamically adapt to the metabolic changes of their microenvironment that are often induced by excess energy intake. Currently, the exact contribution of these macrophages in obesity-driven WAT remodeling remains controversial. Here, using a transgenic CD169-DTR mouse strain, we provide new insights into the interplay between CD169+ adipose tissue macrophages (ATMs) and their surrounding WAT microenvironment. Using targeted in vivo ATM ablation followed by transcriptional and metabolic WAT profiling, we found that ATMs protect WAT from the excessive pathological remodeling that occurs during obesity. As obesity progresses, ATMs control not only vascular integrity, adipocyte function, and lipid and metabolic derangements but also extracellular matrix accumulation and resultant fibrosis in the WAT. The protective role of ATMs during obesity-driven WAT dysfunction supports the notion that ATMs represent friends, rather than foes, as has previously assumed.
| S-EPMC8339675 | biostudies-literature