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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 -
Science (New York, N.Y.) Aug 2017Blood vessels form one of the body's largest surfaces, serving as a critical interface between the circulation and the different organ environments. They thereby exert... (Review)
Review
Blood vessels form one of the body's largest surfaces, serving as a critical interface between the circulation and the different organ environments. They thereby exert gatekeeper functions on tissue homeostasis and adaptation to pathologic challenge. Vascular control of the tissue microenvironment is indispensable in development, hemostasis, inflammation, and metabolism, as well as in cancer and metastasis. This multitude of vascular functions is mediated by organ-specifically differentiated endothelial cells (ECs), whose cellular and molecular heterogeneity has long been recognized. Yet distinct organotypic functional attributes and the molecular mechanisms controlling EC differentiation and vascular bed-specific functions have only become known in recent years. Considering the involvement of vascular dysfunction in numerous chronic and life-threatening diseases, a better molecular understanding of organotypic vasculatures may pave the way toward novel angiotargeted treatments to cure hitherto intractable diseases. This Review summarizes recent progress in the understanding of organotypic vascular differentiation and function.
Topics: Adipose Tissue; Animals; Blood Vessels; Blood-Brain Barrier; Bone and Bones; Capillaries; Cell Differentiation; Endocrine Glands; Endothelium, Vascular; Humans; Kidney; Liver; Lung; Neovascularization, Pathologic; Neovascularization, Physiologic; Retinal Vessels; Transcription, Genetic
PubMed: 28775214
DOI: 10.1126/science.aal2379 -
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 -
International Journal of Surgical... Sep 2020Benign endometrial calcifications with or without bone fragments are uncommon clinicopathologic findings. They can be detected during pelvic ultrasonography or as...
Benign endometrial calcifications with or without bone fragments are uncommon clinicopathologic findings. They can be detected during pelvic ultrasonography or as incidental pathologic findings. They have been found to be associated with infertility and menstrual anomalies in young adult patients and in symptomatic postmenopausal women with endometrial atrophy and endometrial polyps. Its exact etiology is unknown, its pathogenesis is controversial, and its clinical importance is not fully validated. We performed a retrospective review study over 7 years and found 11 (0.4%) cases of benign endometrial calcifications. The mean patient age was 45.2 years (range = 20-66 years). All of the women complained of menstrual abnormalities and 4 complained of infertility. Six had a previous procedure of abortion, 2 had oral contraceptive pills, and 4 a course of progesterone therapy. Their size and morphology varied from heterogeneous microcalcifications of variable appearances, shattered glassy chunks to detached bones. Four cases were associated with endometrial polyps, 1 with a placental site nodule, 1 with chronic endometritis, and 1 with endometrial hyperplasia. Most showed secretory endometrial tissue and ciliated cell metaplasia. Two cases showed atrophic endometrium. Etiology and pathogenesis are multifactorial and miscellaneous. Progesterone may play a role. Heterogeneous histomorphologic patterns may carry potential pitfalls. Pathologic recognition is clinically important to reassure clinicians in symptomatic postmenopausal women, alert gynecologists to a treatable albeit rare cause of infertility in younger women, and assist in patients' counselling. We also included cases of calcifications associated with endometrial malignancies to compare and contrast malignant endometrial calcifications with benign endometrial calcifications.
Topics: Adult; Aged; Calcinosis; Female; Humans; Infertility, Female; Middle Aged; Retrospective Studies; Uterine Diseases; Young Adult
PubMed: 32114859
DOI: 10.1177/1066896920909425 -
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 -
Stroke Apr 2022Ischemic stroke is a leading cause of death and disability worldwide. However, the time window for quickly dissolving clots and restoring cerebral blood flow, using...
BACKGROUND
Ischemic stroke is a leading cause of death and disability worldwide. However, the time window for quickly dissolving clots and restoring cerebral blood flow, using tissue-type plasminogen activator treatment is rather limited, resulting in many patients experiencing long-term functional impairments if not death. This study aims to determine the roles of cranial bone transport (CBT), a novel, effective, and simple surgical technique, in the recovery of ischemic stroke using middle cerebral artery occlusion (MCAO) rat model.
METHODS
CBT was performed by slowly sliding a bone segment in skull with a special frame and a speed of 0.25 mm/12 hours for 10 days following MCAO. Morris water maze, rotarod test, and catwalk gait analysis were used to study the neurological behaviors, and infarct area and cerebral flow were evaluated during CBT process. Immunofluorescence staining of CD31 and Nestin/Sox2 (sex determining region Y box 2) was performed to study the angiogenesis and neurogenesis. OVA-A647 (ovalbumin-Alexa Fluor 647) was intracisterna magna injected to evaluate the meningeal lymphatic drainage function.
RESULTS
CBT treatment has significantly reduced the ischemic lesions areas and improved the neurological deficits in MCAO rats compared with the rats in the control groups. CBT treatment significantly promoted angiogenesis and neurogenesis in the brain of MCAO rats. The drainage function of meningeal lymphatic vessels in MCAO rats was significantly impaired compared with normal rats. Ablation of meningeal lymphatic drainage led to increased neuroinflammation and aggravated neurological deficits and ischemic injury in MCAO rats. CBT treatment significantly improved the meningeal lymphatic drainage function and alleviated T-cell infiltration in MCAO rats.
CONCLUSIONS
This study provided evidence for the possible mechanisms on how CBT attenuates ischemic stroke injury and facilitates rapid neuronal function recovery, suggesting that CBT may be an alternative treatment strategy for managing ischemic stroke.
Topics: Animals; Brain Ischemia; Disease Models, Animal; Humans; Infarction, Middle Cerebral Artery; Ischemic Stroke; Neovascularization, Pathologic; Neurogenesis; Rats; Skull
PubMed: 35135326
DOI: 10.1161/STROKEAHA.121.037912 -
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 -
The Israel Medical Association Journal... Nov 2017Axial spondyloarthritis (axSpA) covers the stage of non-radiographic axial spondyloarthritis (nr-axSpA) and classic ankylosing spondylitis. The pathognomonic findings of... (Review)
Review
Axial spondyloarthritis (axSpA) covers the stage of non-radiographic axial spondyloarthritis (nr-axSpA) and classic ankylosing spondylitis. The pathognomonic findings of axSpA are mainly inflammatory and osteoproliferative changes in the sacroiliac joints (SIJ) and the spine. Various imaging techniques are being used in daily practice for assessment of disease-specific changes, such as periarticular bone marrow edema, erosions, sclerosis, fat metaplasia and ankylosis in the SIJ or spondylitis, spondylodiscitis, facet joint involvement, or syndesmophytes in the spine of patients with axSpA. Conventional radiographs are still considered the gold standard for assessment of structural changes, while the method of for detection of inflammatory changes is magnetic resonance imaging (MRI). A result for an MRI in the SIJ is considered positive for axSpA when more than one lesion is present on one MRI slice, If there is one lesion only, this should be present on at least two consecutive slices. For the spine, inflammatory lesions should preferably be located in the corner of the vertebral bodies, while occurrence of spondylitis in three or more vertebral corners is considered highly suggestive of axSpA. This review gives a detailed overview about the benefits and limitations of all available imaging techniques in patients with axSpA, explains the usage of imaging techniques in the context of diagnosis and differential diagnosis of the disease, and reports on the potential future trends in the area of imaging of the axial skeleton in patients who are suspicious for this diagnosis.
Topics: Diagnosis, Differential; Humans; Magnetic Resonance Imaging; Radiography; Reproducibility of Results; Sacroiliac Joint; Spine; Spondylarthritis
PubMed: 29185288
DOI: No ID Found -
Indian Journal of Ophthalmology Jun 2020
Topics: Humans; Metaplasia
PubMed: 32461466
DOI: 10.4103/ijo.IJO_1829_19