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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 -
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 -
Current Rheumatology Reports Apr 2008Vitamin D is known for its role in calcium homeostasis for optimal skeletal health. It was previously believed that only elderly or hospitalized patients were at risk... (Review)
Review
Vitamin D is known for its role in calcium homeostasis for optimal skeletal health. It was previously believed that only elderly or hospitalized patients were at risk for vitamin D insufficiency, but many people in the general US population have insufficient levels of 25-hydroxyvitamin D (25D). According to the Third National Health and Nutrition Examination Survey, 61% of white and 91% of black Americans suffer from vitamin D insufficiency (25D < 32 ng/mL). Recent studies have demonstrated that a minimum 25(OH)D level of 32 ng/mL is necessary for optimal protection from fracture and intestinal absorption of calcium. Recently, vitamin D has been recognized as important for extraskeletal functions such as immune function, cancer prevention, and hypertension prevention. We review the role of vitamin D in skeletal health and present data on vitamin D in other extraskeletal diseases, with special emphasis on the rheumatology patient.
Topics: Accidental Falls; Bone Density Conservation Agents; Calcium; Ergocalciferols; Fractures, Bone; Humans; Osteogenesis; Rheumatic Diseases; Vitamin D Deficiency
PubMed: 18460265
DOI: 10.1007/s11926-008-0020-y -
International Journal of Molecular... Jun 2022Bone is a highly dynamic tissue that is continuously remodeled to attain and maintain optimal bone integrity, mass, and strength [...].
Bone is a highly dynamic tissue that is continuously remodeled to attain and maintain optimal bone integrity, mass, and strength [...].
Topics: Bone and Bones; Osteoclasts; Osteogenesis
PubMed: 35743101
DOI: 10.3390/ijms23126659 -
European Spine Journal : Official... Oct 2001Osteoinduction is the process by which osteogenesis is induced. It is a phenomenon regularly seen in any type of bone healing process. Osteoinduction implies the... (Review)
Review
Osteoinduction is the process by which osteogenesis is induced. It is a phenomenon regularly seen in any type of bone healing process. Osteoinduction implies the recruitment of immature cells and the stimulation of these cells to develop into preosteoblasts. In a bone healing situation such as a fracture, the majority of bone healing is dependent on osteoinduction. Osteoconduction means that bone grows on a surface. This phenomenon is regularly seen in the case of bone implants. Implant materials of low biocompatibility such as copper, silver and bone cement shows little or no osteoconduction. Osseointegration is the stable anchorage of an implant achieved by direct bone-to-implant contact. In craniofacial implantology, this mode of anchorage is the only one for which high success rates have been reported. Osseointegration is possible in other parts of the body, but its importance for the anchorage of major arthroplasties is under debate. Ingrowth of bone in a porous-coated prosthesis may or may not represent osseointegration.
Topics: Bone Development; Bone and Bones; Humans; Osseointegration; Osteogenesis; Wound Healing
PubMed: 11716023
DOI: 10.1007/s005860100282 -
Endocrine Reviews Nov 2022More than 2.1 million age-related fractures occur in the United States annually, resulting in an immense socioeconomic burden. Importantly, the age-related deterioration... (Review)
Review
More than 2.1 million age-related fractures occur in the United States annually, resulting in an immense socioeconomic burden. Importantly, the age-related deterioration of bone structure is associated with impaired bone healing. Fracture healing is a dynamic process which can be divided into four stages. While the initial hematoma generates an inflammatory environment in which mesenchymal stem cells and macrophages orchestrate the framework for repair, angiogenesis and cartilage formation mark the second healing period. In the central region, endochondral ossification favors soft callus development while next to the fractured bony ends, intramembranous ossification directly forms woven bone. The third stage is characterized by removal and calcification of the endochondral cartilage. Finally, the chronic remodeling phase concludes the healing process. Impaired fracture healing due to aging is related to detrimental changes at the cellular level. Macrophages, osteocytes, and chondrocytes express markers of senescence, leading to reduced self-renewal and proliferative capacity. A prolonged phase of "inflammaging" results in an extended remodeling phase, characterized by a senescent microenvironment and deteriorating healing capacity. Although there is evidence that in the setting of injury, at least in some tissues, senescent cells may play a beneficial role in facilitating tissue repair, recent data demonstrate that clearing senescent cells enhances fracture repair. In this review, we summarize the physiological as well as pathological processes during fracture healing in endocrine disease and aging in order to establish a broad understanding of the biomechanical as well as molecular mechanisms involved in bone repair.
Topics: Humans; Fracture Healing; Bony Callus; Osteogenesis; Fractures, Bone; Cellular Senescence; Aging; Endocrine System Diseases
PubMed: 35182420
DOI: 10.1210/endrev/bnac008 -
ELife Oct 2022The skeletal system contains a series of sophisticated cellular lineages arising from the mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) that...
The skeletal system contains a series of sophisticated cellular lineages arising from the mesenchymal stem cells (MSCs) and hematopoietic stem cells (HSCs) that determine the homeostasis of bone and bone marrow. Here, we reasoned that osteocyte may exert a function in regulation of these lineage cell specifications and tissue homeostasis. Using a mouse model of conditional deletion of osteocytes by the expression of diphtheria toxin subunit α in dentin matrix protein 1 (DMP1)-positive osteocytes, we demonstrated that partial ablation of DMP1-positive osteocytes caused severe sarcopenia, osteoporosis, and degenerative kyphosis, leading to shorter lifespan in these animals. Osteocytes reduction altered mesenchymal lineage commitment, resulting in impairment of osteogenesis and induction of osteoclastogensis. Single-cell RNA sequencing further revealed that hematopoietic lineage was mobilized toward myeloid lineage differentiation with expanded myeloid progenitors, neutrophils, and monocytes, while the lymphopoiesis was impaired with reduced B cells in the osteocyte ablation mice. The acquisition of a senescence-associated secretory phenotype (SASP) in both osteogenic and myeloid lineage cells was the underlying cause. Together, we showed that osteocytes play critical roles in regulation of lineage cell specifications in bone and bone marrow through mediation of senescence.
Topics: Animals; Osteocytes; Osteoblasts; Bone Marrow; Bone and Bones; Osteogenesis
PubMed: 36305580
DOI: 10.7554/eLife.81480 -
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 -
Advanced Drug Delivery Reviews Nov 2015Bone tissue has a remarkable ability to regenerate and heal itself. However, large bone defects and complex fractures still present a significant challenge to the... (Review)
Review
Bone tissue has a remarkable ability to regenerate and heal itself. However, large bone defects and complex fractures still present a significant challenge to the medical community. Current treatments center on metal implants for structural and mechanical support and auto- or allo-grafts to substitute long bone defects. Metal implants are associated with several complications such as implant loosening and infections. Bone grafts suffer from donor site morbidity, reduced bioactivity, and risk of pathogen transmission. Surgical implants can be modified to provide vital biological cues, growth factors and cells in order to improve osseointegration and repair of bone defects. Here we review strategies and technologies to engineer metal surfaces to promote osseointegration with the host tissue. We also discuss strategies for modifying implants for cell adhesion and bone growth via integrin signaling and growth factor and cytokine delivery for bone defect repair.
Topics: Biocompatible Materials; Bone Morphogenetic Protein 2; Bone Regeneration; Bone-Implant Interface; Cytokines; Drug Delivery Systems; Humans; Intercellular Signaling Peptides and Proteins; Osseointegration; Osteogenesis; Polymers; Surface Properties; Tissue Scaffolds
PubMed: 25861724
DOI: 10.1016/j.addr.2015.03.013 -
American Journal of Physiology. Cell... Mar 2022In recent years, technological advances have revealed a large potential number of long noncoding RNAs (lncRNAs). Findings recognize lncRNAs as orchestrating molecules in... (Review)
Review
In recent years, technological advances have revealed a large potential number of long noncoding RNAs (lncRNAs). Findings recognize lncRNAs as orchestrating molecules in a wide range of processes, at the transcriptional and posttranscriptional levels, although fewer studies address function. For differentiation, which consists of rearrangements in the gene expression profile and activation of stage- and cell type-dependent signaling mechanisms, the relevance of lncRNAs becomes crucial. The relationship between lncRNAs and key molecular factors in differentiation is strengthening; therefore the present review aims to comprehensively explain the role of lncRNAs in the signaling network involved in the main types of mesenchymal differentiation: adipogenesis, chondrogenesis, myogenesis, and osteogenesis. Notably, a step toward the integration of lncRNAs in the field of cell differentiation promises an exceptional impact.
Topics: Adipogenesis; Cell Differentiation; Mesenchymal Stem Cells; Osteogenesis; RNA, Long Noncoding
PubMed: 35080923
DOI: 10.1152/ajpcell.00364.2021