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Nature Reviews. Rheumatology Oct 2021Blood vessels form a versatile transport network that is best known for its critical roles in processes such as tissue oxygenation, metabolism and immune surveillance.... (Review)
Review
Blood vessels form a versatile transport network that is best known for its critical roles in processes such as tissue oxygenation, metabolism and immune surveillance. The vasculature also provides local, often organ-specific, molecular signals that control the behaviour of other cell types in their vicinity during development, homeostasis and regeneration, and also in disease processes. In the skeletal system, the local vasculature is actively involved in both bone formation and resorption. In addition, blood vessels participate in inflammatory processes and contribute to the pathogenesis of diseases that affect the joints, such as rheumatoid arthritis and osteoarthritis. This Review summarizes the current understanding of the architecture, angiogenic growth and functional properties of the bone vasculature. The effects of ageing and pathological conditions, including arthritis and osteoporosis, are also discussed.
Topics: Aging; Animals; Arthritis; Bone Development; Bone Diseases; Bone Regeneration; Bone and Bones; Chondrocytes; Endothelium, Vascular; Fractures, Bone; Homeostasis; Humans; Joint Diseases; Macrophages; Mice; Neovascularization, Pathologic; Neovascularization, Physiologic; Osteoblasts; Osteogenesis; Osteoporosis; Receptor Cross-Talk; Synoviocytes
PubMed: 34480164
DOI: 10.1038/s41584-021-00682-3 -
Cells Nov 2022In the physiological condition, the skeletal system's bone resorption and formation are in dynamic balance, called bone homeostasis. However, bone homeostasis is... (Review)
Review
In the physiological condition, the skeletal system's bone resorption and formation are in dynamic balance, called bone homeostasis. However, bone homeostasis is destroyed under pathological conditions, leading to the occurrence of bone metabolism diseases. The expression of hypoxia-inducible factor-1α (HIF-1α) is regulated by oxygen concentration. It affects energy metabolism, which plays a vital role in preventing bone metabolic diseases. This review focuses on the HIF-1α pathway and describes in detail the possible mechanism of its involvement in the regulation of bone homeostasis and angiogenesis, as well as the current experimental studies on the use of HIF-1α in the prevention of bone metabolic diseases. HIF-1α/RANKL/Notch1 pathway bidirectionally regulates the differentiation of macrophages into osteoclasts under different conditions. In addition, HIF-1α is also regulated by many factors, including hypoxia, cofactor activity, non-coding RNA, trace elements, etc. As a pivotal pathway for coupling angiogenesis and osteogenesis, HIF-1α has been widely studied in bone metabolic diseases such as bone defect, osteoporosis, osteonecrosis of the femoral head, fracture, and nonunion. The wide application of biomaterials in bone metabolism also provides a reasonable basis for the experimental study of HIF-1α in preventing bone metabolic diseases.
Topics: Humans; Bone and Bones; Homeostasis; Hypoxia-Inducible Factor 1, alpha Subunit; Metabolic Diseases; Neovascularization, Pathologic
PubMed: 36428981
DOI: 10.3390/cells11223552 -
Theranostics 2021Emerging evidence indicates that the growth of blood vessels and osteogenesis is tightly coordinated during bone development. However, the molecular regulators of...
Emerging evidence indicates that the growth of blood vessels and osteogenesis is tightly coordinated during bone development. However, the molecular regulators of intercellular communication in the bone microenvironment are not well studied. Therefore, we aim to investigate whether BMMSC-Exo promotes osteogenesis and angiogenesis via transporting lnc-H19 in the CBS- heterozygous mouse model. Using RT2 lncRNA PCR array screening, we identify a bone-specific, long noncoding RNA-H19 (lncRNA-H19/lnc-H19) in exosomes derived from bone marrow mesenchymal stem cells (BMMSC-Exo) during osteogenesis. Using bioinformatics analysis, we further discovered the seed sequence of miR-106a that could bind to lnc-H19. A luciferase reporter assay was performed to demonstrate the direct binding of miR-106a to the target gene angiopoietin 1 (Angpt1). We employed an immunocompromised Nude mouse model, to evaluate the effects of BMMSC-Exo on angiogenesis . Using a micro-CT scan, we monitored microstructural changes of bone in the experimental mice. BMMSC-Exo possessed exosomal characteristics including exosome size, and typical markers including CD63, CD9, and TSD101. , BMMSC-Exo significantly promoted endothelial angiogenesis and osteogenesis. Mechanistic studies have shown that exosomal lnc-H19 acts as "sponges" to absorb miR-106 and regulate the expression of angiogenic factor, Angpt1 that activates lnc-H19/Tie2-NO signaling in mesenchymal and endothelial cells. Both of these effects on osteogenesis and angiogenesis are inhibited by antagonizing Tie2 signaling. Treatment of BMMSC-Exo also restored the bone formation and mechanical quality . These findings provide a novel insight into how the extracellular role of exosomal lnc-H19 affects osteogenesis and angiogenesis through competing endogenous RNA networks.
Topics: Angiopoietin-1; Animals; Bone and Bones; Cell Line, Tumor; Endothelial Cells; Exosomes; Genes, Tumor Suppressor; Mesenchymal Stem Cells; Mice; MicroRNAs; Neovascularization, Pathologic; Nitric Oxide; Osteogenesis; RNA, Long Noncoding; Receptor, TIE-2; Signal Transduction
PubMed: 34335960
DOI: 10.7150/thno.58410 -
JCI Insight Apr 2020Increased subchondral bone angiogenesis with blood vessels breaching the tidemark into the avascular cartilage is a diagnostic feature of human osteoarthritis. However,...
Increased subchondral bone angiogenesis with blood vessels breaching the tidemark into the avascular cartilage is a diagnostic feature of human osteoarthritis. However, the mechanisms that initiate subchondral bone angiogenesis remain unclear. We show that abnormally increased platelet-derived growth factor-BB (PDGF-BB) secretion by mononuclear preosteoclasts induces subchondral bone angiogenesis, contributing to osteoarthritis development. In mice after destabilization of the medial meniscus (DMM), aberrant joint subchondral bone angiogenesis developed during an early stage of osteoarthritis, before articular cartilage damage occurred. Mononuclear preosteoclasts in subchondral bone secrete excessive amounts of PDGF-BB, which activates platelet-derived growth factor receptor-β (PDGFR-β) signaling in pericytes for neo-vessel formation. Selective knockout of PDGF-BB in preosteoclasts attenuates subchondral bone angiogenesis and abrogates joint degeneration and subchondral innervation induced by DMM. Transgenic mice that express PDGF-BB in preosteoclasts recapitulate pathological subchondral bone angiogenesis and develop joint degeneration and subchondral innervation spontaneously. Our study provides the first evidence to our knowledge that PDGF-BB derived from preosteoclasts is a key driver of pathological subchondral bone angiogenesis during osteoarthritis development and offers a new avenue for developing early treatments for this disease.
Topics: Animals; Becaplermin; Bone and Bones; Mice; Mice, Inbred C57BL; Neovascularization, Pathologic; Osteoarthritis; Osteoclasts
PubMed: 32208385
DOI: 10.1172/jci.insight.135446 -
Histopathology Feb 2021Owing to a sharp increase in the frequency of diagnosis of colorectal adenomas in the current era of population screening, distinctive morphological features are... (Review)
Review
Owing to a sharp increase in the frequency of diagnosis of colorectal adenomas in the current era of population screening, distinctive morphological features are increasingly being observed. These may present diagnostic challenges and cause clinical management issues. Paneth cell metaplasia is a more common occurrence, but the incidence rates of squamous metaplasia, clear cell metaplasia, osseous metaplasia, neuroendocrine differentiation and signet-ring cell-like lesion are low, and they can be seen in <1% of colorectal adenomas. Their histomorphological characteristics are quite unique; ancillary studies are not very helpful and often not needed. In this review, we give an overview and describe the potential clinical consequences of such incidental and special morphological findings in colorectal adenomas.
Topics: Adenoma; Colorectal Neoplasms; Humans; Incidence; Metaplasia; Neuroendocrine Cells; Ossification, Heterotopic; Paneth Cells
PubMed: 32981102
DOI: 10.1111/his.14263 -
Indian Journal of Ophthalmology Jun 2020
Topics: Humans; Metaplasia
PubMed: 32461466
DOI: 10.4103/ijo.IJO_1829_19 -
CMAJ : Canadian Medical Association... Jun 2022
Topics: Calcinosis; Endometrium; Female; Humans; Infertility; Metaplasia
PubMed: 35760426
DOI: 10.1503/cmaj.220183 -
Annals of Palliative Medicine Feb 2021Tracheobronchopathia osteochondroplastica (TO) is a benign rare disease characterized by multiple tracheobronchial nodules, which has not been clearly illuminated and...
BACKGROUND
Tracheobronchopathia osteochondroplastica (TO) is a benign rare disease characterized by multiple tracheobronchial nodules, which has not been clearly illuminated and there are no standard guidelines for TO management. The aim of this study was to clarify the clinical features and treatment outcomes of TO and provide basis for clinical diagnosis and treatment.
METHODS
A total of 32,215 patients taken bronchoscopy were retrospectively reviewed to select patients diagnosed with TO. Clinical characteristics, bronchoscopic manifestations, CT images, histopathological features, treatments and clinical course were investigated.
RESULTS
13 male and 6 female were identified as TO. The average age was 47.42±12.12 years. The incidence rate of TO in our study by bronchoscopy was 0.06%. The most frequent manifestation was chronic cough. Based on bronchoscopic manifestations, patients were categorized as three groups: the largest proportion was group of Stage II (10/19), followed by Stage III (5/19) and Stage I (4/19). The positive rate of CT in stage I, stage II and stage III was 0%, 50%, 100%, respectively. Histopathological analysis presented inflammatory exudation, squamous metaplasia, submucosal cartilaginous and osseous deposition. Bronchoscopic intervention and inhaled corticosteroids were administered to subjects in stage II and III, which improved their life qualities to some degree.
CONCLUSIONS
Not only multi-disciplinary cooperation of clinical, endoscopic and histological assessment, but also awareness are crucial to TO diagnosis, especially in early stage of TO, which was difficult to identify. The stage of TO based on bronchoscopic visualization might be applied to guide the choice of clinical treatment strategy.
Topics: Adult; Bronchoscopy; Female; Humans; Male; Middle Aged; Osteochondrodysplasias; Retrospective Studies; Tracheal Diseases
PubMed: 33183038
DOI: 10.21037/apm-20-316 -
ACS Applied Bio Materials Jan 2022Craniofacial tissue injuries, diseases, and defects, including those within bone, dental, and periodontal tissues and salivary glands, impact an estimated 1 billion... (Review)
Review
Craniofacial tissue injuries, diseases, and defects, including those within bone, dental, and periodontal tissues and salivary glands, impact an estimated 1 billion patients globally. Craniofacial tissue dysfunction significantly reduces quality of life, and successful repair of damaged tissues remains a significant challenge. Blood vessels and nerves are colocalized within craniofacial tissues and act synergistically during tissue regeneration. Therefore, the success of craniofacial regenerative approaches is predicated on successful recruitment, regeneration, or integration of both vascularization and innervation. Tissue engineering strategies have been widely used to encourage vascularization and, more recently, to improve innervation through host tissue recruitment or prevascularization/innervation of engineered tissues. However, current scaffold designs and cell or growth factor delivery approaches often fail to synergistically coordinate both vascularization and innervation to orchestrate successful tissue regeneration. Additionally, tissue engineering approaches are typically investigated separately for vascularization and innervation. Since both tissues act in concert to improve craniofacial tissue regeneration outcomes, a revised approach for development of engineered materials is required. This review aims to provide an overview of neurovascularization in craniofacial tissues and strategies to target either process thus far. Finally, key design principles are described for engineering approaches that will support both vascularization and innervation for successful craniofacial tissue regeneration.
Topics: Bone and Bones; Humans; Neovascularization, Pathologic; Quality of Life; Tissue Engineering; Wound Healing
PubMed: 35014834
DOI: 10.1021/acsabm.1c00979 -
Cells May 2021Osteosarcoma is the most common primary tumor of the bones affecting mainly young adults. Despite the advances in the field of systemic anticancer therapy, the prognosis... (Review)
Review
Osteosarcoma is the most common primary tumor of the bones affecting mainly young adults. Despite the advances in the field of systemic anticancer therapy, the prognosis of relapsed of metastatic osteosarcoma patients remain dismal with very short survival. However, the better understanding of the pathophysiology of this subtype of sarcoma has led to the identification of new targeted agents with significant activity. In fact, increased angiogenesis plays a major role in the tumor growth and survival of osteosarcoma patients. Several targeted agents have demonstrated a significant anti-tumor activity including multi-kinase inhibitors. In this review, we will discuss the pathophysiology, rationale, and role of targeting angiogenesis via the VEGF pathway in patients with osteosarcoma with emphasis on the published clinical trials and future directions.
Topics: Angiogenesis Inhibitors; Animals; Bone Neoplasms; Humans; Molecular Targeted Therapy; Neovascularization, Pathologic; Osteosarcoma; Protein Kinase Inhibitors; Receptors, Vascular Endothelial Growth Factor; Signal Transduction; Vascular Endothelial Growth Factors
PubMed: 34069999
DOI: 10.3390/cells10051240