scholarly journals Examining the Morphological and Physiological Comparisons of OVX Murine Bone vs. Mini Pigs, Rats, and Humans

2021 ◽  
Vol 10 (3) ◽  
Author(s):  
Shania Jafri ◽  
Karrington Hendrix ◽  
Pedro Cuevas ◽  
Igor Pilawski ◽  
Jill Helms
Keyword(s):  
Bone Matrix ◽  
Bone Diseases ◽  
Skeletal System ◽  
Aging Effects ◽  
Cellular Assays ◽  
Effective Models ◽  
Bone Structures ◽  
Picrosirius Red ◽  
Mini Pigs ◽  
The Three Rs

Osteons are the structure and the base foundation of the human skeletal system. This cylindrical structure contains blood vessels and nerves that supply the bone matrix in humans. To study bone remodeling and bone diseases, mini pigs and rats have mainly been effective models for humans. This study was conducted to examine mouse bone structures in comparison to human, mini pig, and rat bone structures. This addresses the Three Rs principle of clinical testing on animals and proves that mice should be used as models for humans instead of mini pigs and rats. Many scientists prefer not to use mice as models for studying human bone diseases because it has been suggested that their skeletal systems are morphologically and physiologically different–as seen through aging effects. Because mice are easier to produce and can grow at a faster rate, they are more cost and time efficient to use in labs compared to rats and mini pigs. Aniline blue, Ploton silver, picrosirius red stains and TRAP and ALP cellular assays were conducted to analyze bone structures to compare with humans, mini pigs, and rats. Our data did support the hypothesis as explicit similarities between mice bone and other samples such as rats, mini pig, and human was deduced. This study concluded that there were little limitations present by using murine bone as samples for human when studying bone diseases.

Collagen-the Ultrastructural Element of the Bone Matrix

2018 ◽  
Vol 69 (7) ◽  
pp. 1706-1709
Author(s):  
Nicoleta Dumitru ◽  
Andra Cocolos ◽  
Andra Caragheorgheopol ◽  
Constantin Dumitrache ◽  
Ovidiu Gabriel Bratu ◽  
...  
Keyword(s):  
Type I Collagen ◽  
Bone Microarchitecture ◽  
Complex Structure ◽  
Bone Matrix ◽  
Organic Matrix ◽  
Bone Diseases ◽  
Bone Collagen ◽  
Type I ◽  
New Therapeutic Approaches ◽  
And Function

There is an increased interest and more studies highlight the fact that bone strength depends not only on bone tissue quantity, but also on its quality, which is characterized by the geometry and shape of bones, trabecular bone microarchitecture, mineral content, organic matrix and bone turnover. Fibrillar type I collagen is the major organic component of bone matrix, providing form and a stable template for mineralization. The biomedical importance of collagen as a biomaterial for medical and cosmetic purposes and the improvement of the molecular, cellular biology and analytical technologies, led to increasing interest in establishing the structure of this protein and in setting of the relationships between sequence, structure, and function. Bone collagen crosslinking chemistry and its molecular packing structure are considered to be distinct features. This unique post-translational modifications provide to the fibrillar collagen matrices properties such as tensile strength and viscoelasticity. Understanding the complex structure of bone type I collagen as well as the dynamic nature of bone tissues will help to manage new therapeutic approaches to bone diseases.

scholarly journals 18F-Sodium Fluoride PET as a Diagnostic Modality for Metabolic, Autoimmune, and Osteogenic Bone Disorders: Cellular Mechanisms and Clinical Applications

2021 ◽  
Vol 22 (12) ◽  
pp. 6504
Author(s):  
Peter Sang Uk Park ◽  
William Y. Raynor ◽  
Yusha Sun ◽  
Thomas J. Werner ◽  
Chamith S. Rajapakse ◽  
...  
Keyword(s):  
Sodium Fluoride ◽  
Recent Literature ◽  
Imaging Modality ◽  
Bone Diseases ◽  
Skeletal System ◽  
Cellular Mechanisms ◽  
Diagnostic Modality ◽  
Bone Disorders ◽  
Osteoblastic Activity ◽  
Positron Emission

In a healthy body, homeostatic actions of osteoclasts and osteoblasts maintain the integrity of the skeletal system. When cellular activities of osteoclasts and osteoblasts become abnormal, pathological bone conditions, such as osteoporosis, can occur. Traditional imaging modalities, such as radiographs, are insensitive to the early cellular changes that precede gross pathological findings, often leading to delayed disease diagnoses and suboptimal therapeutic strategies. 18F-sodium fluoride (18F-NaF)-positron emission tomography (PET) is an emerging imaging modality with the potential for early diagnosis and monitoring of bone diseases through the detection of subtle metabolic changes. Specifically, the dissociated 18F- is incorporated into hydroxyapatite, and its uptake reflects osteoblastic activity and bone perfusion, allowing for the quantification of bone turnover. While 18F-NaF-PET has traditionally been used to detect metastatic bone disease, recent literature corroborates the use of 18F-NaF-PET in benign osseous conditions as well. In this review, we discuss the cellular mechanisms of 18F-NaF-PET and examine recent findings on its clinical application in diverse metabolic, autoimmune, and osteogenic bone disorders.

scholarly journals Osteomalacia in practice of endocrinologist: etiology, pathogenesis, differential diagnosis with osteoporosis

2020 ◽  
Vol 22 (2) ◽  
pp. 23-31
Author(s):  
Olga O. Golounina ◽  
Gyuzel E. Runova ◽  
Valentin V. Fadeyev
Keyword(s):  
Vitamin D ◽  
Differential Diagnosis ◽  
Vitamin D Deficiency ◽  
Clinical Symptoms ◽  
Fibroblast Growth Factor 23 ◽  
Bone Matrix ◽  
Bone Diseases ◽  
Mineral Density ◽  
Bone Formation Rate ◽  
Metabolic Bone Diseases

Osteoporosis is the most common cause of low bone mineral density (BMD) and low-traumatic fractures in adults. However, differential diagnosis should also consider other causes of decreased BMD, including osteomalacia, as treatment for these conditions vary significantly. Osteomalacia is a systemic disorder characterized by decrease in bone strength due to of excessive accumulation of non-mineralized osteoid and uncoupling between bone matrix formation and mineralization. Osteomalacia in adults mostly develops due to severe vitamin D deficiency of any etiology, less often along with kidney pathology, mesenchymal tumors secreting fibroblast growth factor 23 or hereditary metabolic bone diseases. Clinical symptoms of osteomalacia are nonspecific and mostly manifest by generalized diffuse bone pain, muscle weakness, skeletal deformities and often go unnoticed at initial stage of the disease. Histomorphometric examination is the most accurate method of the diagnosis, which allows assessment of bone formation rate and calcification. The utmost priority of the treatment of osteomalacia of any etiology is the elimination of vitamin D deficiency, hypocalcemia, hypophosphatemia and prevention of bone deformities progression and muscle hypotension.

scholarly journals Plasma Membrane Receptors Involved in the Binding and Response of Osteoclasts to Noncellular Components of the Bone

2021 ◽  
Vol 22 (18) ◽  
pp. 10097
Author(s):  
Divakar S. Karanth ◽  
Macey L. Martin ◽  
Lexie S. Holliday
Keyword(s):  
Bone Cells ◽  
Bone Matrix ◽  
Bone Diseases ◽  
Membrane Receptors ◽  
Membrane Structures ◽  
Regulatory Effects ◽  
Plasma Membrane Receptors ◽  
To Receive ◽  
New Strategies

Osteoclasts differentiate from hematopoietic cells and resorb the bone in response to various signals, some of which are received directly from noncellular elements of the bone. In vitro, adherence to the bone triggers the reduction of cell–cell fusion events between osteoclasts and the activation of osteoclasts to form unusual dynamic cytoskeletal and membrane structures that are required for degrading the bone. Integrins on the surface of osteoclasts are known to receive regulatory signals from the bone matrix. Regulation of the availability of these signals is accomplished by enzymatic alterations of the bone matrix by protease activity and phosphorylation/dephosphorylation events. Other membrane receptors are present in osteoclasts and may interact with as yet unidentified signals in the bone. Bone mineral has been shown to have regulatory effects on osteoclasts, and osteoclast activity is also directly modulated by mechanical stress. As understanding of how osteoclasts and other bone cells interact with the bone has emerged, increasingly sophisticated efforts have been made to create bone biomimetics that reproduce both the structural properties of the bone and the bone’s ability to regulate osteoclasts and other bone cells. A more complete understanding of the interactions between osteoclasts and the bone may lead to new strategies for the treatment of bone diseases and the production of bone biomimetics to repair defects.

scholarly journals Dynamic Collision Behavior Between Osteoblasts and Tumor Cells Regulates the Disordered Arrangement of Collagen Fiber/Apatite Crystals in Metastasized Bone

2018 ◽  
Vol 19 (11) ◽  
pp. 3474 ◽  
Author(s):  
Aira Matsugaki ◽  
Tatsuki Harada ◽  
Yumi Kimura ◽  
Aiko Sekita ◽  
Takayoshi Nakano
Keyword(s):  
Bone Tissue ◽  
Tumor Cells ◽  
Collagen Fiber ◽  
Molecular Mechanisms ◽  
Ex Vivo ◽  
Bone Matrix ◽  
Bone Diseases ◽  
Mechanical Function ◽  
Metastasis Model ◽  
Tissue Anisotropy

Bone metastasis is one of the most intractable bone diseases; it is accompanied with a severe mechanical dysfunction of bone tissue. We recently discovered that the disorganized collagen/apatite microstructure in cancer-bearing bone is a dominant determinant of the disruption of bone mechanical function; disordered osteoblast arrangement was found to be one of the principal determinants of the deteriorated collagen/apatite microstructure. However, the precise molecular mechanisms regulating the disordered osteoblast arrangement triggered by cancer invasion are not yet understood. Herein, we demonstrate a significant disorganization of bone tissue anisotropy in metastasized bone in our novel ex vivo metastasis model. Further, we propose a novel mechanism underlying the disorganization of a metastasized bone matrix: A dynamic collision behavior between tumor cells and osteoblasts disturbs the osteoblast arrangement along the collagen substrate.

scholarly journals Interleukin-17A Interweaves the Skeletal and Immune Systems

2021 ◽  
Vol 11 ◽  
Author(s):  
Mengjia Tang ◽  
Lingyun Lu ◽  
Xijie Yu
Keyword(s):  
Inflammatory Cells ◽  
Bone Diseases ◽  
Dual Role ◽  
Skeletal System ◽  
Interleukin 17A ◽  
Immune Mediated ◽  
Skeletal Homeostasis ◽  
Axial Spondylarthritis

The complex crosstalk between the immune and the skeletal systems plays an indispensable role in the maintenance of skeletal homeostasis. Various cytokines are involved, including interleukin (IL)-17A. A variety of immune and inflammatory cells produces IL-17A, especially Th17 cells, a subtype of CD4+ T cells. IL-17A orchestrates diverse inflammatory and immune processes. IL-17A induces direct and indirect effects on osteoclasts. The dual role of IL-17A on osteoclasts partly depends on its concentrations and interactions with other factors. Interestingly, IL-17A exerts a dual role in osteoblasts in vitro. IL-17A is a bone-destroying cytokine in numerous immune-mediated bone diseases including postmenopausal osteoporosis (PMOP), rheumatoid arthritis (RA), psoriatic arthritis (PsA) and axial spondylarthritis (axSpA). This review will summarize and discuss the pathophysiological roles of IL-17A on the skeletal system and its potential strategies for application in immune-mediated bone diseases.

The Osteocyte as a Signaling Cell

2021 ◽  
Author(s):  
Jesus Medical Delgado-Calle ◽  
Teresita Bellido
Keyword(s):  
Bone Cells ◽  
Bone Matrix ◽  
Bone Diseases ◽  
Bone Homeostasis ◽  
Marrow Fat ◽  
Effector Cells ◽  
Beneficial Effects ◽  
Mineralized Bone Matrix ◽  
And Function ◽  
Endocrine Signaling

Osteocytes, former osteoblasts encapsulated by mineralized bone matrix, are far from being passive and metabolically inactive bone cells. Instead, osteocytes are multifunctional and dynamic cells capable of integrating hormonal and mechanical signals and transmitting them to effector cells in bone as well as in distant tissues. Osteocytes are a significant source of molecules that regulate bone homeostasis by integrating mechanical cues and hormonal signals that coordinate the differentiation and function of osteoclasts and osteoblasts. Osteocyte function is altered in rare and common bone diseases, suggesting that osteocyte dysfunction is directly involved in the pathophysiology of disorders affecting the skeleton. Advances in osteocyte biology initiated the development of novel therapeutics interfering with osteocyte secreted molecules. Moreover, osteocytes are targets and key distributors of biological signals mediating the beneficial effects of various bone therapeutics used in the clinic. Herein, we review the most recent discoveries in osteocyte biology demonstrating that osteocytes regulate bone homeostasis and bone marrow fat via paracrine signaling, influence body composition and energy metabolism via endocrine signaling, and contribute to the damaging effects of diabetes mellitus and hematological and metastatic cancers in the skeleton.

Control of osteocyte dendrite formation by Sp7 and its target gene osteocrin

2021 ◽  
Author(s):  
Jialiang S Wang ◽  
Tushar Kamath ◽  
Fatemeh Mirzamohammadi ◽  
Daniel Rotter ◽  
Hironori Hojo ◽  
...  
Keyword(s):  
Gene Networks ◽  
Target Gene ◽  
Target Genes ◽  
Bone Matrix ◽  
Bone Diseases ◽  
Dendrite Formation ◽  
Skeletal Disease ◽  
Mineralized Bone Matrix

Osteocytes use an elaborate network of dendritic connections to control bone remodeling. Some osteoblasts embed within mineralized bone matrix, change shape, and become osteocytes. The molecular circuitry that drives dendrite formation during "osteocytogenesis" is poorly understood. Here we show that deletion of Sp7, a gene linked to rare and common skeletal disease, in mature osteoblasts and osteocytes causes severe defects in osteocyte dendrites. Unbiased profiling of Sp7 target genes and binding sites reveals unexpected repurposing of this transcription factor to drive dendrite formation. Osteocrin is a Sp7 target gene that promotes osteocyte dendrite formation and rescues phenotypic and molecular defects in Sp7-deficient mice. Single-cell RNA-sequencing demonstrates overt defects in osteocyte maturation in vivo in the absence of Sp7. Sp7-dependent gene networks enriched in developing osteocytes are associated with rare and common human skeletal traits. Moreover, humans homozygous for the osteogenesis imperfecta-causing SP7R316C mutation show dramatic defects in osteocyte morphology. Genes that mark osteocytes in vivo and that are regulated by Sp7 in vitro are highly enriched in neurons, highlighting shared features between osteocytic and neuronal connectivity. Taken together, these findings reveal a crucial role for Sp7 and its target gene Osteocrin in osteocytogenesis, demonstrating that pathways that control osteocyte development influence human bone diseases.

Alpinetin Inhibits RANKL-Induced Osteoclastogenesis and Ovariectomy-Induced Bone Loss by Modulating NFATc1 Transcription and Lysosomal Function

2020 ◽  
Author(s):  
Rongxin He ◽  
Jinwei Lu ◽  
Yazhou Chen ◽  
Yong Li ◽  
Chenyi Ye ◽  
...  
Keyword(s):  
Bone Resorption ◽  
Bone Loss ◽  
Bone Matrix ◽  
Osteoclast Differentiation ◽  
Estrogen Deficiency ◽  
Bone Diseases ◽  
Dependent Manner ◽  
Metabolic Bone Diseases ◽  
Lysosomal Function ◽  
Metabolic Bone

Abstract BackgroundPostmenopausal osteoporosis is a chronic metabolic bone disease caused by excessive osteoclast activation, and osteoclasts are considered to be the sole participants in the degeneration and resorption of bone matrix for controlling bone integrity and continuity. The biological functions of osteoclasts depend critically on the number and activity of fused polykaryon. Hence, targeting osteoclast differentiation and activity can modulate bone resorption and alleviate osteoporosis. Alpinetin is widely used for excellent anti-inflammatory activities and little side-effect, but its role in osteoporosis remains unknown.ResultsIn this study, we investigated for the first time the ability of alpinetin to inhibit estrogen deficiency-induced bone loss. Alpinetin significantly reduced the expression levels of NFATc1 and its downstream genes, thereby inhibiting osteoclast differentiation in a concentration- and time-dependent manner. Additionally, alpinetin inhibited F-actin ring formation and bone resorption, as well as reduced the activation levels of NF-κB, ERK, and AKT signaling cascades. In mature osteoclasts, alpinetin remarkably inhibited integrin-mediated migration and lysosomal biogenesis and trafficking by modulating the PKCβ/TFEB and ATG5/LC3 axes. Importantly, alpinetin treatment in mice alleviated ovariectomy-induced bone volume loss. ConclusionOur findings strongly suggest that alpinetin plays a significant role in the regulation of NFATc1 production for the differentiation of osteoclasts and inhibits integrin-mediated cell migration and lysosomal function in mature osteoclasts, thus weaken the increased osteolytic ability due to estrogen deficiency. Alpinetin may represent a promising agent for the treatment of osteoporosis and other metabolic bone diseases.

In Vivo Live Imaging of Bone Using Shortwave Infrared Fluorescence Quantum Dots

2020 ◽  
Author(s):  
Yanjun Che ◽  
Sijia Feng ◽  
Jiangbo Guo ◽  
Junjun Hou ◽  
Xuesong Zhu ◽  
...  
Keyword(s):  
Ex Vivo ◽  
Biological Activities ◽  
Imaging Techniques ◽  
Critical Role ◽  
Specific Interaction ◽  
Live Imaging ◽  
Bone Diseases ◽  
Imaging Results ◽  
Bone Structures

Abstract Bone is playing an increasingly critical role in human health and disease. More noninvasive multi-scale imaging techniques are urgently required for investigations on the substructures and biological functions of bones. Our results firstly revealed that our prepared SWIR QDs acted as a bone-specific image contrast to achieve real-time imaging of bone structures both in vivo and ex vivo. The major bone structures of both Balb/C nude mouse and Balb/C mouse including the skull, spine, pelvis, limbs and the sternum could be rapidly and gradually identified via blood circulation after QDs injection in vivo. More importantly, the binding capability of our QDs mainly depend on the biological activities of bone tissues, suggesting our technique was suitable for in vivo live imaging. Additionally, the cell imaging results suggested that the potential mechanism of our bone imaging could be ascribed to the highly specific interaction between QDs and MC3T3-E1 cells. In a word, skeletal structures and biological activities of bones are anticipated to be observed and monitored with this QDs-guided SWIR imaging strategy, respectively. This radiation-free QDs-guided SWIR live imaging of bone can put new insights into a comprehensive study of bones in vivo and provide basis for early diagnosis of bone diseases.

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