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International Journal of Molecular... May 2016The clinical need for effective bone regeneration therapy remains in huge demands. However, the current "gold standard" treatments of autologous and allogeneic bone... (Review)
Review
The clinical need for effective bone regeneration therapy remains in huge demands. However, the current "gold standard" treatments of autologous and allogeneic bone grafts may result in various complications. Furthermore, safety considerations of biomaterials and cell-based treatment require further clarification. Therefore, developing new therapies with stronger osteogenic potential and a lower incidence of complications is worthwhile. Recently, exosomes, small vesicles of endocytic origin, have attracted attention in bone regeneration field. The vesicles travel between cells and deliver functional cargoes, such as proteins and RNAs, thereby regulating targeted cells differentiation, commitment, function, and proliferation. Much evidence has demonstrated the important roles of exosomes in osteogenesis both in vitro and in vivo. In this review, we summarize the properties, origins and biogenesis of exosomes, and the recent reports using exosomes to regulate osteogenesis and promote bone regeneration.
Topics: Animals; Bone Regeneration; Exosomes; Humans; Neovascularization, Physiologic; Osteogenesis
PubMed: 27213355
DOI: 10.3390/ijms17050712 -
Tissue Engineering and Regenerative... Apr 2022Restoration of the bone defects caused by infection or disease remains a challenge in orthopedic surgery. In recent studies, scaffold-free engineered tissue with a...
BACKGROUND
Restoration of the bone defects caused by infection or disease remains a challenge in orthopedic surgery. In recent studies, scaffold-free engineered tissue with a self-secreted extracellular matrix has been proposed as an alternative strategy for tissue regeneration and reconstruction. Our study aimed to engineer and fabricate self-assembled osteogenic and scaffold-free tissue for bone regeneration.
METHODS
Osteogenic scaffold-free tissue was engineered and fabricated using fetal cartilage-derived progenitor cells, which are capable of osteogenic differentiation. They were cultured in osteogenic induction environments or using demineralized bone powder for differentiation. The fabricated tissue was subjected to real-time qPCR, biochemical, and histological analyses to estimate the degree of in vitro osteogenic differentiation. To demonstrate bone formation in an in vivo environment, scaffold-free tissue was transplanted into the dorsal subcutaneous site of nude mice. Bone development was monitored postoperatively over 8 weeks by the observation of calcium deposition in the matrix.
RESULTS
In the in vitro experiments, engineered osteogenically induced scaffold-free tissue demonstrated three-dimensional morphological characteristics, and sufficient osteogenic differentiation was confirmed through the quantification of specific osteogenic gene markers expressed and calcium accumulation within the matrix. Following the evaluation of differentiation efficacy, in vivo experiments revealed distinct bone formation, and that blood vessels had penetrated the fabricated tissue.
CONCLUSION
The novel engineering of scaffold-free tissue with osteogenic potential can be used as an optimal bone graft substitute for bone regeneration.
Topics: Animals; Bone Regeneration; Mesenchymal Stem Cells; Mice; Mice, Nude; Osteogenesis; Tissue Scaffolds
PubMed: 35122585
DOI: 10.1007/s13770-021-00418-0 -
Annals of the New York Academy of... Mar 2010Osteocytes are derived from osteoblasts and make up over 90% of the cells in bone. However, the mechanisms that control the differentiation of osteoblasts into... (Review)
Review
Osteocytes are derived from osteoblasts and make up over 90% of the cells in bone. However, the mechanisms that control the differentiation of osteoblasts into osteocytes embedded in bone matrix are not well understood. With the recent developments of transgenic models for manipulating gene expression in osteocytes and of transgenic mice carrying lineage reporters for osteoblasts and osteocytes, unprecedented new insights are becoming possible. In this article we review recent advances, such as comparative gene and protein expression studies, that are delineating the changes in gene and protein expression that accompany osteocyte differentiation. We also review recent studies in which time-lapse dynamic imaging approaches have been used to visualize osteoblast and osteocyte populations within bone. These approaches reveal the key role of cell motility in bone cell function and highlight the dynamic nature of mineralized tissues. Changes in motile properties of the cell may be key in the transition from osteoblast to osteocyte, as reflected in the altered expression of many molecules involved in cytoskeletal function.
Topics: Animals; Cell Differentiation; Cell Movement; Genes, Developmental; Humans; Kinetics; Mice; Models, Biological; Organ Specificity; Osteoblasts; Osteocytes; Osteogenesis
PubMed: 20392270
DOI: 10.1111/j.1749-6632.2009.05246.x -
Rheumatology (Oxford, England) Mar 2020Enthesitis is a key manifestation of PsA and current knowledge supports the concept that it may be among the primary events in the development of this disease, as well... (Review)
Review
Enthesitis is a key manifestation of PsA and current knowledge supports the concept that it may be among the primary events in the development of this disease, as well as other forms of SpA. Patients with PsA seem to have a different threshold to mechanical stress, which may be genetically determined. Hence patients with psoriatic disease respond pathologically with inflammation after being exposed to physiological mechanical stress. Activation of pro-inflammatory mediators such as IL-17 and TNF-α as well as the influx of innate immune cells are key events in the development of enthesitis in PsA. Chronic entheseal inflammation is accompanied by new bone formation, leading to bony spurs in peripheral (entheseophytes) and axial (syndesmophytes) structures. This article reviews the current knowledge on the mechanisms involved in the development of enthesitis in patients with PsA.
Topics: Arthritis, Psoriatic; Enthesopathy; Humans; Inflammation; Interleukin-17; Interleukin-23; Osteogenesis; Stress, Mechanical; Tumor Necrosis Factor-alpha
PubMed: 32159793
DOI: 10.1093/rheumatology/keaa039 -
Bone May 2023FBXO11 is the substrate-recognition component of a ubiquitin ligase complex called SKP1-cullin-F-boxes. The role of FBXO11 in bone development is unexplored. In this...
FBXO11 is the substrate-recognition component of a ubiquitin ligase complex called SKP1-cullin-F-boxes. The role of FBXO11 in bone development is unexplored. In this study, we reported a novel mechanism of how bone development is regulated by FBXO11. FBXO11 gene knockdown by lentiviral transduction in mouse pre-osteoblast MC3T3-E1 cells leads to reduced osteogenic differentiation, while overexpressing FBXO11 accelerates their osteogenic differentiation in vitro. Furthermore, we generated two osteoblastic-specific FBXO11 conditional knockout mouse models, Col1a1-ERT2-FBXO11KO and Bglap2-FBXO11KO mice. In both conditional FBXO11KO mouse models, we found FBXO11 deficiency inhibits normal bone growth, in which the osteogenic activity in FBXO11cKO mice is reduced, while osteoclastic activity is not significantly changed. Mechanistically, we found FBXO11 deficiency leads to Snail1 protein accumulation in osteoblasts, leading to suppression of osteogenic activity and inhibition of bone matrix mineralization. FBXO11 knockdown in MC3T3-E1 cells reduced Snail1 protein ubiquitination and increased Snail1 protein accumulation in the cells, which eventually inhibited osteogenic differentiation. In conclusion, FBXO11 deficiency in osteoblasts inhibits bone formation through Snail1 accumulation, inhibiting osteogenic activity and bone mineralization.
Topics: Animals; Mice; Osteogenesis; Cell Differentiation; Calcification, Physiologic; Osteoclasts; Osteoblasts
PubMed: 36863499
DOI: 10.1016/j.bone.2023.116709 -
Journal of Dental Research Mar 2022The primary cilium is a nonmotile microtubule-based organelle in most vertebrate cell types. The primary cilium plays a critical role in tissue development and...
The primary cilium is a nonmotile microtubule-based organelle in most vertebrate cell types. The primary cilium plays a critical role in tissue development and homeostasis by sensing and transducing various signaling pathways. Ciliary proteins such as intraflagellar transport (IFT) proteins as well as ciliary motor proteins, kinesin and dynein, comprise a bidirectional intraflagellar transport system needed for cilia formation and function. Mutations in ciliary proteins that lead to loss or dysfunction of primary cilia cause ciliopathies such as Jeune syndrome and Ellis-van Creveld syndrome and cause abnormalities in tooth development. These diseases exhibit severe skeletal and craniofacial dysplasia, highlighting the significance of primary cilia in skeletal development. Cilia are necessary for the propagation of hedgehog, transforming growth factor β, platelet-derived growth factor, and fibroblast growth factor signaling during osteogenesis and chondrogenesis. Ablation of ciliary proteins such as IFT80 or IFT20 blocks cilia formation, which inhibits osteoblast differentiation, osteoblast polarity, and alignment and reduces bone formation. Similarly, cilia facilitate chondrocyte differentiation and production of a cartilage matrix. Cilia also play a key role in mechanosensing and are needed for increased bone formation in response to mechanical forces.
Topics: Bone and Bones; Cartilage; Cilia; Fibroblast Growth Factors; Osteogenesis
PubMed: 34743626
DOI: 10.1177/00220345211046606 -
Journal of Nanobiotechnology Oct 2021Titanium (Ti) implants are widely used in dentistry and orthopedics owing to their excellent corrosion resistance, biocompatibility, and mechanical properties, which... (Review)
Review
Titanium (Ti) implants are widely used in dentistry and orthopedics owing to their excellent corrosion resistance, biocompatibility, and mechanical properties, which have gained increasing attention from the viewpoints of fundamental research and practical applications. Also, numerous studies have been carried out to fine-tune the micro/nanostructures of Ti and/or incorporate chemical elements to improve overall implant performance. Zinc oxide nanoparticles (nano-ZnO) are well-known for their good antibacterial properties and low cytotoxicity along with their ability to synergize with a variety of substances, which have received increasingly widespread attention as biomodification materials for implants. In this review, we summarize recent research progress on nano-ZnO modified Ti-implants. Their preparation methods of nano-ZnO modified Ti-implants are introduced, followed by a further presentation of the antibacterial, osteogenic, and anti-corrosion properties of these implants. Finally, challenges and future opportunities for nano-ZnO modified Ti-implants are proposed.
Topics: Anti-Bacterial Agents; Corrosion; Lasers; Nanoparticles; Nanostructures; Nanotubes; Osteogenesis; Prostheses and Implants; Surface Properties; Titanium; Zinc Oxide
PubMed: 34717648
DOI: 10.1186/s12951-021-01099-6 -
PloS One 2018Distraction osteogenesis is an effective method for generating large amounts of bone in situ for treating pathologies such as large bone defects or skeletal...
Distraction osteogenesis is an effective method for generating large amounts of bone in situ for treating pathologies such as large bone defects or skeletal malformations, for instance leg-length discrepancies. While an optimized distraction procedure might have the potential to reduce the rate of complications significantly, our knowledge of the underlying mechanobiological processes is still insufficient for systematic optimization of treatment parameters such as distraction rate or fixation stiffness. We present a novel numerical model of lateral distraction osteogenesis, based on a mechanically well-controlled in vivo experiment. This model extends an existing numerical model of callus healing with viscoplastic material properties for describing stress relaxation and stimuli history-dependent tissue differentiation, incorporating delay and memory effects. A reformulation of appositional growth based non-local biological stimuli in terms of spatial convolution as well as remeshing and solution-mapping procedures allow the model to cope with severe mesh distortions associated with large plastic deformations. With these enhancements, our model is capable of replicating the in vivo observations for lateral distraction osteogenesis in sheep using the same differentiation rules and the same set of parameters that successfully describes callus healing in sheep, indicating that tissue differentiation hypotheses originally developed for fracture healing scenarios might indeed be applicable to distraction as well. The response of the model to modified distraction parameters corresponds to existing studies, although the currently available data is insufficient for rigorous validation. As such, this study provides a first step towards developing models that can serve as tools for identifying both interesting research questions and, eventually, even optimizing clinical procedures once better data for calibration and validation becomes available.
Topics: Algorithms; Animals; Bony Callus; Computer Simulation; Fracture Healing; Leg Length Inequality; Models, Biological; Osteogenesis; Osteogenesis, Distraction; Stress, Mechanical
PubMed: 29543908
DOI: 10.1371/journal.pone.0194500 -
Scanning 2018Bone repair materials are rapidly becoming a hot topic in the field of biomedical materials due to being an important means of repairing human bony deficiencies and... (Review)
Review
Bone repair materials are rapidly becoming a hot topic in the field of biomedical materials due to being an important means of repairing human bony deficiencies and replacing hard tissue. Magnesium (Mg) alloys are potentially biocompatible, osteoconductive, and biodegradable metallic materials that can be used in bone repair due to their in situ degradation in the body, mechanical properties similar to those of bones, and ability to positively stimulate the formation of new bones. However, rapid degradation of these materials in physiological environments may lead to gas cavities, hemolysis, and osteolysis and thus, hinder their clinical orthopedic applications. This paper reviews recent work on the use of Mg alloy implants in bone repair. Research to date on alloy design, surface modification, and biological performance of Mg alloys is comprehensively summarized. Future challenges for and developments in biomedical Mg alloys for use in bone repair are also discussed.
Topics: Absorbable Implants; Alloys; Bone Diseases; Bone Substitutes; Humans; Magnesium Compounds; Osteogenesis
PubMed: 29725492
DOI: 10.1155/2018/9216314 -
European Spine Journal : Official... Oct 2001The aim of this review is to describe major approaches for stimulating bone healing and to review other factors affecting bone healing. Spinal bone fusion after surgery... (Review)
Review
The aim of this review is to describe major approaches for stimulating bone healing and to review other factors affecting bone healing. Spinal bone fusion after surgery is a demanding process requiring optimal conditions for clinical success. Bone formation and healing can be enhanced through various methods. Experimental studies have revealed an array of stimulative measures. These include biochemical stimulation by use of hormones and growth factors, physical stimulation through mechanical and electromagnetic measures, and bone grafting by use of bone tissue or bone substitutes. Newer biological techniques such as stem cell transplantation and gene therapy can also be used to stimulate bone healing. Apart from bone transplantation, clinical experience with the many stimulation modalities is limited. Possible areas for clinical use of these novel methods are discussed.
Topics: Aging; Animals; Bone Transplantation; Bone and Bones; Growth Substances; Humans; Osteogenesis; Wound Healing
PubMed: 11716006
DOI: 10.1007/s005860100269