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Cell Metabolism Feb 2023Mitochondrial components have been abundantly detected in bone matrix, implying that they are somehow transported extracellularly to regulate osteogenesis. Here, we...
Mitochondrial components have been abundantly detected in bone matrix, implying that they are somehow transported extracellularly to regulate osteogenesis. Here, we demonstrate that mitochondria and mitochondrial-derived vesicles (MDVs) are secreted from mature osteoblasts to promote differentiation of osteoprogenitors. We show that osteogenic induction stimulates mitochondrial fragmentation, donut formation, and secretion of mitochondria through CD38/cADPR signaling. Enhancing mitochondrial fission and donut formation through Opa1 knockdown or Fis1 overexpression increases mitochondrial secretion and accelerates osteogenesis. We also show that mitochondrial fusion promoter M1, which induces Opa1 expression, impedes osteogenesis, whereas osteoblast-specific Opa1 deletion increases bone mass. We further demonstrate that secreted mitochondria and MDVs enhance bone regeneration in vivo. Our findings suggest that mitochondrial morphology in mature osteoblasts is adapted for extracellular secretion, and secreted mitochondria and MDVs are critical promoters of osteogenesis.
Topics: Osteogenesis; Mitochondria; Osteoblasts; Mitochondrial Dynamics; Cell Differentiation
PubMed: 36754021
DOI: 10.1016/j.cmet.2023.01.003 -
International Journal of Biological... 2021Both osteoblasts and preosteoclasts contribute to the coupling of osteogenesis and angiogenesis, regulating bone regeneration. Astragaloside IV (AS-IV), a glycoside of...
Both osteoblasts and preosteoclasts contribute to the coupling of osteogenesis and angiogenesis, regulating bone regeneration. Astragaloside IV (AS-IV), a glycoside of cycloartane-type triterpene derived from the Chinese herb , exhibits various biological activities, including stimulating angiogenesis and attenuating ischemic-hypoxic injury. However, the effects and underlying mechanisms of AS-IV in osteogenesis, osteoclastogenesis, and bone regeneration remain poorly understood. In the present study, we found that AS-IV treatment inhibited osteoclastogenesis, preserved preosteoclasts, and enhanced platelet-derived growth factor-BB (PDGF-BB)-induced angiogenesis. Additionally, AS-IV promoted cell viability, osteogenic differentiation, and angiogenic gene expression in bone marrow mesenchymal stem cells (BMSCs). The activation of AKT/GSK-3β/β-catenin signaling was found to contribute to the effects of AS-IV on osteoclastogenesis and osteogenesis. Furthermore, AS-IV accelerated bone regeneration during distraction osteogenesis (DO), as evidenced from the improved radiological and histological manifestations and biomechanical parameters, accompanied by enhanced angiogenesis within the distraction zone. In summary, AS-IV accelerates bone regeneration during DO, by enhancing osteogenesis and preosteoclast-induced angiogenesis simultaneously, partially through AKT/GSK-3β/β-catenin signaling. These findings reveal that AS-IV may serve as a potential bioactive molecule for promoting the coupling of osteogenesis and angiogenesis, and imply that AKT/GSK-3β/β-catenin signaling may be a promising therapeutic target for patients during DO treatment.
Topics: Animals; Bone Marrow; Bone Regeneration; Cell Proliferation; Cells, Cultured; Drugs, Chinese Herbal; Male; Models, Animal; Neovascularization, Physiologic; Osteoblasts; Osteogenesis; Rats; Rats, Sprague-Dawley; Saponins; Triterpenes
PubMed: 33994865
DOI: 10.7150/ijbs.57681 -
International Journal of Oral Science Jan 2022Distraction osteogenesis (DO) is widely used for bone tissue engineering technology. Immune regulations play important roles in the process of DO like other bone... (Review)
Review
Distraction osteogenesis (DO) is widely used for bone tissue engineering technology. Immune regulations play important roles in the process of DO like other bone regeneration mechanisms. Compared with others, the immune regulation processes of DO have their distinct features. In this review, we summarized the immune-related events including changes in and effects of immune cells, immune-related cytokines, and signaling pathways at different periods in the process of DO. We aim to elucidated our understanding and unknowns about the immunomodulatory role of DO. The goal of this is to use the known knowledge to further modify existing methods of DO, and to develop novel DO strategies in our unknown areas through more detailed studies of the work we have done.
Topics: Bone Regeneration; Bone and Bones; Osteogenesis; Osteogenesis, Distraction; Tissue Engineering
PubMed: 35067679
DOI: 10.1038/s41368-021-00156-y -
Materials Science & Engineering. C,... Oct 2019Bone fracture healing is a multistep and overlapping process of inflammation, angiogenesis and osteogenesis. It is initiated by inflammation, causing the release of... (Review)
Review
Bone fracture healing is a multistep and overlapping process of inflammation, angiogenesis and osteogenesis. It is initiated by inflammation, causing the release of various cytokines and growth factors. It leads to the recruitment of stem cells and formation of vasculature resulting in the functional bone formation. This combined phenomenon is used by bone tissue engineers from past few years to address the problem of vasculature and osteogenic differentiation during bone regeneration. In this review, we have discussed all major studies reporting the dual functioning approach to promote osteogenesis coupled angiogenesis using various scaffolds. These scaffolds are broadly classified into four types based on the nature of their structural and functional components. The functionality of the scaffold is either due to the structural components or the loaded cargo which conducts or induces the coupled functionality. Dual delivery system for osteoinductive and angioinductive factors ensures the co-delivery of two different types of molecules to induce osteogenesis and angiogenesis. Single delivery scaffold for angioinductive and osteoinductive molecule releases single type of molecules which could induce both angiogenesis and osteogenesis. Osteoconductive scaffold consisted of bone constituents releases angioinductive factors. Osteoconductive and angioconductive scaffold composed of components which provide the native substrate features for osteogenesis and angiogenesis. This review article also discusses the studies highlighting the synergism of physico-chemical stimuli as dual functioning feature to enhance angiogenesis and osteogenesis simultaneously. In addition, this article covers one of the least discussed area of the bone regeneration i.e. 'cartilage formation as a median between angiogenesis and osteogenesis'.
Topics: Animals; Biocompatible Materials; Bone Regeneration; Bone and Bones; Humans; Intercellular Signaling Peptides and Proteins; Neovascularization, Physiologic; Osteogenesis; Tissue Engineering; Tissue Scaffolds; Trace Elements
PubMed: 31349418
DOI: 10.1016/j.msec.2019.109761 -
Differentiation; Research in Biological... 2023The vascular system plays a crucial role in bone tissue. Angiogenic and osteogenic processes are coupled through a spatial-temporal connection. Recent studies have... (Review)
Review
The vascular system plays a crucial role in bone tissue. Angiogenic and osteogenic processes are coupled through a spatial-temporal connection. Recent studies have identified three types of capillaries in the skeletal system. Compared with type L and E vessels, type H vessels express high levels of CD31 and endomucin, and function to couple angiogenesis and osteogenesis. Endothelial cells in type H vessels interact with osteolineage cells (e.g., osteoblasts, osteoclasts, and osteocytes) through cytokines or signaling pathways to maintain bone growth and homeostasis. In imbalanced bone homeostases, such as osteoporosis and osteoarthritis, it may be a new therapeutic strategy to regulate the endothelial cell activity in type H vessels to repair the imbalance. Here, we reviewed the latest progress in relevant factors or signaling pathways in coupling angiogenesis and osteogenesis. This review would contribute to further understanding the role and mechanisms of type H vessels in coupling angiogenic and osteogenic processes. Furthermore, it will facilitate the development of therapeutic approaches for bone disorders by targeting type H vessels.
Topics: Osteogenesis; Endothelial Cells; Neovascularization, Physiologic; Bone and Bones; Homeostasis
PubMed: 37774549
DOI: 10.1016/j.diff.2023.09.005 -
Developmental Dynamics : An Official... Aug 2013Angiogenesis is likely critical for the process of intramembranous osteogenesis; however, the developmental relationship between blood vessels and bone mineralization is... (Review)
Review
BACKGROUND
Angiogenesis is likely critical for the process of intramembranous osteogenesis; however, the developmental relationship between blood vessels and bone mineralization is not well studied within intramembranous bones. Given its importance, changes in angiogenesis regulation are likely to contribute to evolutionarily and medically relevant craniofacial variation.
RESULTS
We summarize what is known about the association between angiogenesis and intramembranous osteogenesis, supplementing with information from the better-studied processes of endochondral ossification and distraction osteogenesis. Based on this review, we introduce a model of angiogenesis during early intramembranous osteogenesis as well as a series of null hypotheses to be tested.
CONCLUSIONS
This model can serve as a basis of future research on the spatio-temporal association and regulatory interactions of mesenchymal, vascular, and bone cells, which will be required to illuminate the potential effects of angiogenesis dysregulation on craniofacial skeletal phenotypes.
Topics: Animals; Humans; Muscle, Skeletal; Neovascularization, Physiologic; Osteogenesis
PubMed: 23737393
DOI: 10.1002/dvdy.23992 -
Experimental & Molecular Medicine Nov 2022The mammalian skeletal system is densely innervated by both neural and vascular networks. Peripheral nerves in the skeleton include sensory and sympathetic nerves. The... (Review)
Review
The mammalian skeletal system is densely innervated by both neural and vascular networks. Peripheral nerves in the skeleton include sensory and sympathetic nerves. The crosstalk between skeletal and neural tissues is critical for skeletal development and regeneration. The cellular processes of osteogenesis and angiogenesis are coupled in both physiological and pathophysiological contexts. The cellular and molecular regulation of osteogenesis and angiogenesis have yet to be fully defined. This review will provide a detailed characterization of the regulatory role of nerves and blood vessels during bone regeneration. Furthermore, given the importance of the spatial relationship between nerves and blood vessels in bone, we discuss neurovascular coupling during physiological and pathological bone formation. A better understanding of the interactions between nerves and blood vessels will inform future novel therapeutic neural and vascular targeting for clinical bone repair and regeneration.
Topics: Animals; Neurovascular Coupling; Vascular Endothelial Growth Factor A; Bone Regeneration; Osteogenesis; Bone and Bones; Neovascularization, Physiologic; Mammals
PubMed: 36446849
DOI: 10.1038/s12276-022-00899-6 -
Advances in Space Biology and Medicine 2002
Review
Topics: Animals; Bone Resorption; Gravity, Altered; Humans; Osteogenesis; Space Flight
PubMed: 12951696
DOI: 10.1016/s1569-2574(02)08018-8 -
Advanced Healthcare Materials Feb 2019Biomaterials with suitable surface modification strategies are contributing significantly to the rapid development of the field of bone tissue engineering. Despite these... (Review)
Review
Biomaterials with suitable surface modification strategies are contributing significantly to the rapid development of the field of bone tissue engineering. Despite these encouraging results, utilization of biomaterials is poorly translated to human clinical trials potentially due to lack of knowledge about the interaction between biomaterials and the body defense mechanism, the "immune system". The highly complex immune system involves the coordinated action of many immune cells that can produce various inflammatory and anti-inflammatory cytokines. Besides, bone fracture healing initiates with acute inflammation and may later transform to a regenerative or degenerative phase mainly due to the cross-talk between immune cells and other cells in the bone regeneration process. Among various immune cells, macrophages possess a significant role in the immune defense, where their polarization state plays a key role in the wound healing process. Growing evidence shows that the macrophage polarization state is highly sensitive to the biomaterial's physiochemical properties, and advances in biomaterial research now allow well controlled surface properties. This review provides an overview of biomaterial-mediated modulation of the immune response for regulating key bone regeneration events, such as osteogenesis, osteoclastogenesis, and inflammation, and it discusses how these strategies can be utilized for future bone tissue engineering applications.
Topics: Animals; Biocompatible Materials; Bone Regeneration; Humans; Immunologic Factors; Osteogenesis; Tissue Engineering
PubMed: 30328293
DOI: 10.1002/adhm.201801106 -
Nature Biomedical Engineering Jul 2019
Topics: Animals; Cell Culture Techniques; Cell Differentiation; Collagen Type I; Collagen Type I, alpha 1 Chain; Humans; Induced Pluripotent Stem Cells; Mesenchymal Stem Cells; Mice; Mice, Inbred NOD; Mice, SCID; Mutation; Osteogenesis; Phenotype; Tretinoin; X-Ray Microtomography
PubMed: 31278386
DOI: 10.1038/s41551-019-0422-3