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International Journal of Molecular... Apr 2020Bone loss raises great concern in numerous situations, such as ageing and many diseases and in both orthopedic and dentistry fields of application, with an extensive... (Review)
Review
Bone loss raises great concern in numerous situations, such as ageing and many diseases and in both orthopedic and dentistry fields of application, with an extensive impact on health care. Therefore, it is crucial to understand the mechanisms and the determinants that can regulate osteogenesis and ensure bone balance. Autophagy is a well conserved lysosomal degradation pathway, which is known to be highly active during differentiation and development. This review provides a revision of the literature on all the exogen factors that can modulate osteogenesis through autophagy regulation. Metal ion exposition, mechanical stimuli, and biological factors, including hormones, nutrients, and metabolic conditions, were taken into consideration for their ability to tune osteogenic differentiation through autophagy. In addition, an exhaustive overview of biomaterials, both for orthopedic and dentistry applications, enhancing osteogenesis by modulation of the autophagic process is provided as well. Already investigated conditions regulating bone regeneration via autophagy need to be better understood for finely tailoring innovative therapeutic treatments and designing novel biomaterials.
Topics: Autophagy; Biocompatible Materials; Biological Factors; Cell Differentiation; Dentistry; Humans; Lysosomes; Metals; Orthopedics; Osteogenesis; Signal Transduction
PubMed: 32316424
DOI: 10.3390/ijms21082789 -
Tissue & Cell Jun 2023Macrophages (MΦ) are highly adaptable and functionally polarized cells that play a crucial role in various physiological and pathological processes. Typically, MΦ... (Review)
Review
Macrophages (MΦ) are highly adaptable and functionally polarized cells that play a crucial role in various physiological and pathological processes. Typically, MΦ differentiate into two distinct subsets: the proinflammatory (M1) and anti-inflammatory (M2) phenotypes. Due to their potent immunomodulatory and anti-inflammatory properties, MΦ have garnered significant attention in recent decades. In the context of bone implant repair, the immunomodulatory function of MΦ is of paramount importance. Depending on their polarization phenotype, MΦ can exert varying effects on osteogenesis, angiogenesis, and the inflammatory response around the implant. This paper provides an overview of the immunomodulatory and inflammatory effects of MΦ polarization in the repair of bone implants.
Topics: Cell Differentiation; Macrophages; Phenotype; Osteogenesis
PubMed: 37257287
DOI: 10.1016/j.tice.2023.102112 -
Experimental Physiology Mar 2023What is the topic of this review? In this review, we consider the key role of mitochondria in the peri-implant milieu, including the regulation of mitochondrial reactive... (Review)
Review
NEW FINDINGS
What is the topic of this review? In this review, we consider the key role of mitochondria in the peri-implant milieu, including the regulation of mitochondrial reactive oxygen species and mitochondrial metabolism in angiogenesis, the polarization of macrophage immune responses, and bone formation and bone resorption during osseointegration. What advances does it highlight? Mitochondria contribute to the behaviours of peri-implant cell lines based on metabolic and reactive oxygen species signalling modulations, which will contribute to the research field and the development of new treatment strategies for improving implant success.
ABSTRACT
Osseointegration is a dynamic biological process in the local microenvironment adjacent to a bone implant, which is crucial for implant performance and success of the implant surgery. Recently, the role of mitochondria in the peri-implant microenvironment during osseointegration has gained much attention. Mitochondrial regulation has been verified to be essential for cellular events in osseointegration and as a therapeutic target for peri-implant diseases in the peri-implant microenvironment. In this review, we summarize our current knowledge of the key role of mitochondria in the peri-implant milieu, including the regulation of mitochondrial reactive oxygen species and mitochondrial metabolism in angiogenesis, the polarization of macrophage immune responses, and bone formation and resorption during osseointegration, which will contribute to the research field and the development of new treatment strategies to improve implant success. In addition, we indicate limitations in our current understanding of the regulation of mitochondria in osseointegration and suggest topics for further study.
Topics: Humans; Reactive Oxygen Species; Bone and Bones; Osteogenesis; Bone Resorption; Osseointegration; Mitochondria
PubMed: 36648334
DOI: 10.1113/EP090988 -
Current Osteoporosis Reports Dec 2023Here, we discuss the origin of chondrocytes, their destiny, and their plasticity in relationship to bone growth, articulation, and formation of the trabeculae. We also... (Review)
Review
PURPOSE OF REVIEW
Here, we discuss the origin of chondrocytes, their destiny, and their plasticity in relationship to bone growth, articulation, and formation of the trabeculae. We also consider these processes from a biological, clinical, and evolutionary perspective.
RECENT FINDINGS
Chondrocytes, which provide the template for the formation of most bones, are responsible for skeletal growth and articulation during postnatal life. In recent years our understanding of the fate of these cells has changed dramatically. Current evidence indicates a paradoxical situation during skeletogenesis, with some cells of mesenchymal condensation differentiating directly into osteoblasts, whereas others of the same kind give rise to highly similar osteoblasts via a complex process of differentiation involving several chondrocyte intermediates. The situation becomes even more paradoxical during postnatal growth when stem cells in the growth plate produce differentiated, functional progenies, which thereafter presumably dedifferentiate into another type of stem cell. Such a remarkable transition from one cell type to another under postnatal physiological conditions provides a fascinating example of cellular plasticity that may have valuable clinical implications.
Topics: Humans; Chondrocytes; Cell Plasticity; Osteogenesis; Bone Development; Bone and Bones; Osteoblasts; Growth Plate; Cell Differentiation
PubMed: 37837512
DOI: 10.1007/s11914-023-00827-1 -
Journal of Cellular and Molecular... Feb 2024Blood vessels are essential for bone development and metabolism. Type H vessels in bone, named after their high expression of CD31 and Endomucin (Emcn), have recently... (Review)
Review
Blood vessels are essential for bone development and metabolism. Type H vessels in bone, named after their high expression of CD31 and Endomucin (Emcn), have recently been reported to locate mainly in the metaphysis, exhibit different molecular properties and couple osteogenesis and angiogenesis. A strong correlation between type H vessels and bone metabolism is now well-recognized. The crosstalk between type H vessels and osteoprogenitor cells is also involved in bone metabolism-related diseases such as osteoporosis, osteoarthritis, fracture healing and bone defects. Targeting the type H vessel formation may become a new approach for managing a variety of bone diseases. This review highlighted the roles of type H vessels in bone-related diseases and summarized the research attempts to develop targeted intervention, which will help us gain a better understanding of their potential value in clinical application.
Topics: Humans; Osteogenesis; Bone and Bones; Osteoporosis; Bone Diseases, Metabolic; Fracture Healing; Neovascularization, Physiologic
PubMed: 38353470
DOI: 10.1111/jcmm.18123 -
Annals of the Rheumatic Diseases Feb 2024This study aimed to identify the types and heterogeneity of cells within the spinal enthesis and investigate the underlying mechanisms of osteogenesis.
OBJECTIVES
This study aimed to identify the types and heterogeneity of cells within the spinal enthesis and investigate the underlying mechanisms of osteogenesis.
METHODS
Single-cell RNA sequencing was used to identify cell populations and their gene signatures in the spinal enthesis of five patients with ankylosing spondylitis (AS) and three healthy individuals. The transcriptomes of 40 065 single cells were profiled and divided into 7 clusters: neutrophils, monocytic cells, granulomonocytic progenitor_erythroblasts, T cells, B cells, plasma cells and stromal cells. Real-time quantitative PCR, immunofluorescence, flow cytometry, osteogenesis induction, alizarin red staining, immunohistochemistry, short hairpin RNA and H&E staining were applied to validate the bioinformatics analysis.
RESULTS
Pseudo-time analysis showed two differentiation directions of stromal cells from the mesenchymal stem cell subpopulation MSC-C2 to two Cxcl12-abundant-reticular (CAR) cell subsets, Osteo-CAR and Adipo-CAR, within which three transcription factors, C-JUN, C-FOS and CAVIN1, were highly expressed in AS and regulated the osteogenesis of mesenchymal stem cells. A novel subcluster of early-stage neutrophils, CD99_G1, was elevated in AS. The proinflammatory characteristics of monocyte dendritic cell progenitor-recombinant adiponectin receptor 2 monocytic cells were explored. Interactions between Adipo-CAR cells, CD99_G1 neutrophils and other cell types were mapped by identifying ligand-receptor pairs, revealing the recruitment characteristics of CD99_G1 neutrophils by Adipo-CAR cells and the pathogenesis of osteogenesis induced in AS.
CONCLUSIONS
Our results revealed the dynamics of cell subpopulations, gene expression and intercellular interactions during AS pathogenesis. These findings provide new insights into the cellular and molecular mechanisms of osteogenesis and will benefit the development of novel therapeutic strategies.
Topics: Humans; Cell Differentiation; Cells, Cultured; Mesenchymal Stem Cells; Neutrophils; Osteogenesis; Spondylitis, Ankylosing
PubMed: 37977819
DOI: 10.1136/ard-2023-224107 -
Genomics Sep 2023To investigate EGR1-mediated METTL3/m6A/CHI3L1 axis in osteoporosis.
OBJECTIVE
To investigate EGR1-mediated METTL3/m6A/CHI3L1 axis in osteoporosis.
METHODS
Ovariectomy (OVX) was performed on mice to induce osteoporosis, followed by μ-CT scanning of femurs, histological staining, immunohistochemistry analysis of MMP9 and NFATc1, and ELISA of serum BGP, ALP, Ca, and CTXI. The isolated mouse bone marrow mononuclear macrophages (BMMs) were differentiated into osteoclasts under cytokine stimulation. TRAP staining was performed to quantify osteoclasts. The levels of Nfatc1, c-Fos, Acp5, and Ctsk in osteoclasts, m6A level, and the relationships among EGR1, METTL3, and CHI3L1 were analyzed.
RESULTS
The EGR1/METTL3/CHI3L1 levels and m6A level were upregulated in osteoporotic mice and the derived BMMs. EGR1 was a transcription factor of METTL3. METTL3 promoted the post-transcriptional regulation of CHI3L1 by increasing m6A methylation. EGR1 downregulation reduced BMMs-differentiated osteoclasts and alleviated OVX-induced osteoporosis by regulating the METTL3/m6A/CHI3L1 axis.
CONCLUSION
EGR1 promotes METTL3 transcription and increases m6A-modified CHI3L1 level, thereby stimulating osteoclast differentiation and osteoporosis development.
Topics: Animals; Female; Mice; Cell Differentiation; Macrophages; NFATC Transcription Factors; Osteoclasts; Osteogenesis; Osteoporosis; Proto-Oncogene Proteins c-fos
PubMed: 37558013
DOI: 10.1016/j.ygeno.2023.110696 -
Frontiers in Immunology 2023Determining the transcriptomes and molecular mechanism underlying human degenerative nucleus pulposus (NP) is of critical importance for treating intervertebral disc...
BACKGROUND AND AIMS
Determining the transcriptomes and molecular mechanism underlying human degenerative nucleus pulposus (NP) is of critical importance for treating intervertebral disc degeneration (IDD). Here, we aimed to elucidate the detailed molecular mechanism of NP ossification and IDD using single-cell RNA sequencing.
METHODS
Single-cell RNA-seq and bioinformatic analysis were performed to identify NP cell populations with gene signatures, biological processes and pathways, and subpopulation analysis, RNA velocity analysis, and cell-to-cell communication analysis were performed in four IDD patients. We also verified the effects of immune cells on NP ossification using cultured NP cells and a well-established rat IDD model.
RESULTS
We identified five cell populations with gene expression profiles in degenerative NP at single-cell resolution. GO database analysis showed that degenerative NP-associated genes were mainly enriched in extracellular matrix organization, immune response, and ossification. Gene set enrichment analysis showed that rheumatoid arthritis signaling, antigen processing and presentation signaling were activated in the blood cell cluster. We revealed that stromal cells, which are progenitor cells, differentiated toward an ossification phenotype and delineated interactions between immune cells (macrophages and T cells) and stromal cells. Immune factors such as TNF-α, CD74 and CCL-3 promoted the differentiation of stromal cells toward an ossification phenotype . Blocking TNF-α with a specific inhibitor successfully reversed NP ossification and modified NP morphology .
CONCLUSION
Our study revealed an increase in macrophages and T cells in degenerative NP, which induced stromal cell differentiation toward an ossification phenotype, and contributed to the identification of a novel therapeutic target to delay IDD.
Topics: Humans; Animals; Rats; Nucleus Pulposus; Osteogenesis; Single-Cell Gene Expression Analysis; Tumor Necrosis Factor-alpha; Cell Differentiation
PubMed: 37638033
DOI: 10.3389/fimmu.2023.1224627 -
Nature Communications Jul 2022The ontogeny and fate of stem cells have been extensively investigated by lineage-tracing approaches. At distinct anatomical sites, bone tissue harbors multiple types of...
The ontogeny and fate of stem cells have been extensively investigated by lineage-tracing approaches. At distinct anatomical sites, bone tissue harbors multiple types of skeletal stem cells, which may independently supply osteogenic cells in a site-specific manner. Periosteal stem cells (PSCs) and growth plate resting zone stem cells (RZSCs) critically contribute to intramembranous and endochondral bone formation, respectively. However, it remains unclear whether there is functional crosstalk between these two types of skeletal stem cells. Here we show PSCs are not only required for intramembranous bone formation, but also for the growth plate maintenance and prolonged longitudinal bone growth. Mice deficient in PSCs display progressive defects in intramembranous and endochondral bone formation, the latter of which is caused by a deficiency in PSC-derived Indian hedgehog (Ihh). PSC-specific deletion of Ihh impairs the maintenance of the RZSCs, leading to a severe defect in endochondral bone formation in postnatal life. Thus, crosstalk between periosteal and growth plate stem cells is essential for post-developmental skeletal growth.
Topics: Animals; Chondrocytes; Growth Plate; Hedgehog Proteins; Mice; Osteogenesis; Stem Cells
PubMed: 35851381
DOI: 10.1038/s41467-022-31592-x -
Current Opinion in Biotechnology Aug 2022In recent years it has been increasingly appreciated that blood vessels are not simply suppliers of nutrients and oxygen, but actually play an exquisite regulatory role... (Review)
Review
In recent years it has been increasingly appreciated that blood vessels are not simply suppliers of nutrients and oxygen, but actually play an exquisite regulatory role in bone development and repair. A specialized kind of endothelium, named type H because of its high expression of CD31 and Endomucin, constitutes anatomically defined vessels in proximity of the epiphyseal growth plate. Type H endothelium regulates the proliferation and differentiation of both osteoblasts and osteoclasts through the secretion of angiocrine signals and is a hub for the bidirectional molecular crosstalk between the different cell populations of the osteogenic microenvironment. Type H vessels are a key target for current translational approaches aiming at coupling angiogenesis and osteogenesis for bone repair. Open questions remain about their presence and features in notstereotyped tissues, like engineered osteogenic grafts, and the opportunities for their clinical stimulation by pharmacological treatments.
Topics: Bone Regeneration; Cell Differentiation; Osteogenesis; Signal Transduction
PubMed: 35841865
DOI: 10.1016/j.copbio.2022.102750