Current Approaches of Bone Morphogenetic Proteins in Dentistry

2015 ◽  
Vol 41 (3) ◽  
pp. 337-342 ◽  
Author(s):  
Rosa-María Díaz-Sánchez ◽  
Rosa-María Yáñez-Vico ◽  
Ana Fernández-Olavarría ◽  
Regina Mosquera-Pérez ◽  
Alejandro Iglesias-Linares ◽  
...  
Keyword(s):  
Bone Morphogenetic Proteins ◽  
Specific Growth ◽  
Bone Matrix ◽  
Bone Lesions ◽  
Allogenic Bone ◽  
Bone Morphogenic Proteins ◽  
Alloplastic Materials ◽  
Bone Response ◽  
Near Future

Bone morphogenic proteins (BMPs) are a group of osteoinductive proteins obtained from nonmineralized bone matrix; they are capable of stimulating the differentiation of pluripotent mesenchymal cells to osteoprogenitor cells. They have become a likely treatment option, given their action on regeneration and remodeling of bone lesions and increasing the bone response around alloplastic materials. It may be feasible in the near future for BMPs to replace autologous and allogenic bone grafts. The application of specific growth factors for osteoinduction without using a bone graft constitutes a real impact on bone regeneration. The use of BMP is not only focused on osteogenic regeneration: There are a variety of studies investigating other properties, such as periodontal or dental regeneration from the conservative viewpoint. In this review, we will highlight the role of the BMP in bone, periodontal and dental regeneration.

Nf1 Plays an Essential Role in Osteoclasts Development Via Hyperactivation of Ras- PI3K Signaling.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 1462-1462
Author(s):  
Shi Chen ◽  
David A. Ingram ◽  
Mary Jo Wenning ◽  
Janet Hock ◽  
Feng-Chun Yang ◽  
...  
Keyword(s):  
Solid Phase ◽  
Bone Matrix ◽  
Bone Lesions ◽  
Pi3k Signaling ◽  
Lytic Enzymes ◽  
Enzyme Activity Assay ◽  
Skeletal Defects ◽  
Deficient Mice

Abstract Patients with neurofibromatosis type 1 (NF1) have mutations in the NF1 tumor-suppressor gene that functions as a GTPase activating protein (GAP) for p21ras. Individuals with NF1 display a variety of skeletal defects including lytic bone lesions. However, the effect of loss of NF1 on osteoclasts or osteoblasts, the two principal cells involved in bone remodeling, is not understood. Osteoclasts are specialized myeloid cells that adhere to bone matrix, and secrete lytic enzymes that degrade bone. Given that we have previously identified haploinsufficient phenotypes in Nf1 +/− mast cells, we defined the role of neurofibromin in regulating various osteoclast functions in vitro and in vivo in Nf1 +/− mice. Strikingly, histologic sections from femurs of Nf1 +/− mice, revealed large numbers of multinucleated osteoclasts. This phenotype is reminiscent of the osteoclasts in patients with Paget’s disease and of osteoclasts isolated from SHIP deficient mice, which have elevated levels of PI-3K activity. Additionally, osteoclast progenitors from Nf1 +/− mice were hyperresponsive to limiting concentrations of M-CSF and RANKL and formed higher numbers of OCL progenitors compared to +/+ controls (P<0.05). M-CSF binding to its receptor (c-fms) causes a rapid increase in p21ras activity. Nf1 +/− osteoclasts had higher basal and M-CSF-stimulated p21ras-GTP levels compared to wild type cells. The Ras-PI3K- pathway has been implicated in controlling numerous osteoclast functions. An increase in basal and M-CSF stimulated Akt activation, a sensitive indicator of PI3-K activity, was observed in Nf1 +/− osteoclasts. Since a key initiating component of the resorptive process of osteoclasts is their ability to bind to αv B3 on the bone surface, we next examined whether haploinsufficiency of Nf1 altered adhesion by culturing osteoclasts on αv B3 coated plates. Nf1 +/− osteoclasts had a significant increase in adhesion to αv B3 compared to wildtype controls. Osteoclasts were then cultured onto bone slices and the number and size of the resorption pits were scored. Nf1 +/− osteoclasts have a higher frequency of forming pits as compared to wildtype controls and additionally the area of each pit was significantly greater. Further, a solid phase immunofixed-enzyme activity assay that measures bone resorption revealed that Nf1 +/− mice had a 2 fold increase in activity as compared to WT controls. Consistent with this activity, Nf1 +/− femurs required less stress to fracture in biomechanical testing. Further, utilizing a genetic intercross between Nf1+/− and Class1A PI3K deficient mice (p85α), we demonstrate that the increased number of osteoclast progenitors, as well as the increased hypersensitivity of Nf1 +/− osteoclast progenitors to M-CSF and RANKL were corrected to WT levels in progenitors that are mutant at both the Nf1 and the p85α loci. Additionally, the gain in function in the proliferation, migration, adhesion, and lytic activity of Nf1 +/− osteoclasts is mediated via the Ras-PI3K signaling axis. Collectively, these studies provide novel insights into the role of neurofibromin in regulating a lineage that may contribute to skeletal abnormalities in individuals with NF1.

DNA methylation in satellite repeats disorders

2019 ◽  
Vol 63 (6) ◽  
pp. 757-771 ◽  
Author(s):  
Claire Francastel ◽  
Frédérique Magdinier
Keyword(s):  
Dna Methylation ◽  
Human Genome ◽  
Repetitive Dna ◽  
Dna Sequences ◽  
Satellite Repeats ◽  
Tremendous Progress ◽  
Genes Encoding ◽  
Dna Elements ◽  
Near Future

Abstract Despite the tremendous progress made in recent years in assembling the human genome, tandemly repeated DNA elements remain poorly characterized. These sequences account for the vast majority of methylated sites in the human genome and their methylated state is necessary for this repetitive DNA to function properly and to maintain genome integrity. Furthermore, recent advances highlight the emerging role of these sequences in regulating the functions of the human genome and its variability during evolution, among individuals, or in disease susceptibility. In addition, a number of inherited rare diseases are directly linked to the alteration of some of these repetitive DNA sequences, either through changes in the organization or size of the tandem repeat arrays or through mutations in genes encoding chromatin modifiers involved in the epigenetic regulation of these elements. Although largely overlooked so far in the functional annotation of the human genome, satellite elements play key roles in its architectural and topological organization. This includes functions as boundary elements delimitating functional domains or assembly of repressive nuclear compartments, with local or distal impact on gene expression. Thus, the consideration of satellite repeats organization and their associated epigenetic landmarks, including DNA methylation (DNAme), will become unavoidable in the near future to fully decipher human phenotypes and associated diseases.

Overview of Biological Therapy in Ulcerative Colitis: Current and Future Directions

2015 ◽  
Vol 24 (2) ◽  
pp. 203-213 ◽  
Author(s):  
Federica Furfaro ◽  
Cristina Bezzio ◽  
Sandro Ardizzone ◽  
Alessandro Massari ◽  
Roberto De Franchis ◽  
...  
Keyword(s):  
Ulcerative Colitis ◽  
Immunosuppressive Agents ◽  
Mucosal Healing ◽  
Aminosalicylic Acid ◽  
Proinflammatory Mediators ◽  
Experimental Drugs ◽  
New Treatments ◽  
Aggressive Clinical Course ◽  
Near Future

The treatment of ulcerative colitis (UC) has changed over the last decade. It is extremely important to optimize the therapies which are available nowadays and commonly used in daily clinical practice, as well as to stimulate the search for more powerful drugs for the induction and maintenance of sustained and durable remission, thus preventing further complications. Therefore, it is mandatory to identify the patients' prognostic variables associated with an aggressive clinical course and to test the most potent therapies accordingly.To date, the conventional therapeutic approach based on corticosteroids, salicylates (sulfasalazine, 5-aminosalicylic acid) or immunosuppressive agents is commonly used as a first step to induce and to maintain remission. However, in recent years, knowledge of new pathogenetic mechanisms of ulcerative colitis have allowed us to find new therapeutic targets leading to the development of new treatments that directly target proinflammatory mediators, such as TNF-alpha, cytokines, membrane migration agents, cellular therapies.The aim of this review is to provide the most significant data regarding the therapeutic role of drugs in UC and to give an overview of biological and experimental drugs that will become available in the near future. In particular, we will analyse the role of these drugs in the treatment of acute flare and maintenance of UC, as well as its importance in mucosal healing and in treating patients at a high risk of relapse.

Potential role of an endothelium-specific growth factor, hepatocyte growth factor, on endothelial damage in diabetes

Diabetes ◽  
1997 ◽  
Vol 46 (1) ◽  
pp. 138-142 ◽  
Author(s):  
R. Morishita ◽  
S. Nakamura ◽  
Y. Nakamura ◽  
M. Aoki ◽  
A. Moriguchi ◽  
...  
Keyword(s):  
Growth Factor ◽  
Hepatocyte Growth Factor ◽  
Potential Role ◽  
Specific Growth ◽  
Endothelial Damage ◽  
Specific Growth Factor ◽  
Hepatocyte Growth

Potential Role of Cytokines in Children with Acute Appendicitis and Acute Mesenteric Lymphadenitis

2011 ◽  
Vol 11 (1) ◽  
pp. 130-133
Author(s):  
Astra Zviedre ◽  
Arnis Engelis ◽  
Mohit Kakar ◽  
Aigars Pētersons
Keyword(s):  
Early Detection ◽  
Acute Appendicitis ◽  
Inflammatory Mediators ◽  
Potential Role ◽  
Clinical Symptoms ◽  
Future Research ◽  
Mesenteric Lymphadenitis ◽  
Proper Diagnosis ◽  
Near Future

Potential Role of Cytokines in Children with Acute Appendicitis and Acute Mesenteric Lymphadenitis Although, AAP and AML have different etiological factors, clinical symptoms are very much similar but treatment tactics in both the disease differ a lot. In case of AML, treatment is more conservative and does not require hospitalization while in case of AAP immediate hospitalization and maybe further surgery can be mandatory. With the identification of group of cytokines serum inflammatory mediators IL-8, IL-10, IL-12[p70], IL-17, TNF-a and MCP-1, it is believed early and proper diagnosis of AAP in the near future. Research of cytokines-serum inflammatory mediators has opened new opportunities for an early detection and differentiation of these two diseases in children.

A Review on Ethnobotanical, Phytochemical, Pharmacological and Traditional Aspects of Indigenous Indian Herb Trachyspermum ammi (L)

2020 ◽  
Vol 6 (3) ◽  
pp. 172-187 ◽  
Author(s):  
Nikita Saraswat ◽  
Neetu Sachan ◽  
Phool Chandra
Keyword(s):  
Chemical Constituents ◽  
Collective Data ◽  
Trachyspermum Ammi ◽  
Present Information ◽  
Gastrointestinal Problems ◽  
Vedic Literature ◽  
Key Terms ◽  
Phytochemical Studies ◽  
Near Future

Introduction and Ethnopharmacological relevance: In the Indian Vedic literature, Charakasamhita and Sushritasamhita, the Ajwain is known as Bhootika and in the charaksamhita commentaries, it is termed as Yavanika. The medicinal role of Ajwain fruit is claimed to be very important in the treatment of many ailments in humans. The plant Trachyspermum ammi Linn. is a grassy, aromatic annual plant, which falls in the family Umbelliferae. This plant is grown in India, Iran, Pakistan, Egypt, etc. for its medicinal benefits. Tribals of India use it for the treatment of diarrhea, arthritis, colic and gastrointestinal problems. In the traditional preparations, Indian Vaidya guru’s (Ayurveda Guru’s), the ajwain extract is used as “Admoda Arka”. The Ayurveda doctors, hakims and Vaidya gurus recommend ajwain for treating headaches, cold, flu and even during painful menstrual periods. Aim of the Study: The review paper has compiled the researches conducted on Trachyspermum ammi, which will help in presenting a collective data of the authentic researches conducted on the plant worldwide. It will also present information about the phytoconstituents which can be useful for building up new researches in near future. Materials and Methods: This paper has been prepared by collecting all the information available on the following platforms and the papers were searched from 1975 to 2019. The databases and electronic journals were well searched including Wiley, Springer link, Google Scholar, Science Direct, Pubmed. The key terms used for the search were Ajwain, C. copticum, Trachyspermum ammi and other synonyms of the plant. The search was also done by the names of chemical constituents present in the plant and the pharmacological effect of the plant. Results: The multiple uses of T. ammi are due to the active constituents present in it. As per the phytochemical studies on the fruits of T. ammi, the presence of various phytoconstituents has been found such as saponins, flavonoids, alkaloids, glycosides, fixed oils, thymenes, cumenes, tannins, amino acids, p-cymene, c-terpinene, steroids, etc. Conclusions: This paper is focused on presenting a detailed review on the literature, pharmacological properties, physicochemical studies and the newest researches on the plant. In this paper, we have also compiled the traditional uses of the herb used by Indian peopleon recommendations from their Hakims, Vaidya and use of the herbs by many tribes all across India and Pakistan.

scholarly journals Simultaneity and Precise Time in Rotation

Universe ◽  
2019 ◽  
Vol 5 (12) ◽  
pp. 226 ◽  
Author(s):  
Don Koks
Keyword(s):  
Time Coordinate ◽  
Near Future ◽  
Precise Time ◽  
Made In

I analyse the role of simultaneity in relativistic rotation by building incrementally on its role in simpler scenarios. Historically, rotation has been analysed in 1 + 1 dimensions; but my stance is that a 2 + 1 -dimensional treatment is necessary. This treatment requires a discussion of what constitutes a frame, how coordinate choices differ from frame choices, and how poor coordinates can be misleading. I determine how precisely we are able to define a meaningful time coordinate on a gravity-free rotating Earth, and discuss complications due to gravity on our real Earth. I end with a critique of several statements made in relativistic precision-timing literature, that I maintain contradict the tenets of relativity. Those statements tend to be made in the context of satellite-based navigation; but they are independent of that technology, and hence are not validated by its success. I suggest that if relativistic precision-timing adheres to such analyses, our civilian timing is likely to suffer in the near future as clocks become ever more precise.

scholarly journals Genetic and epigenetic mechanisms in the development of congenital heart diseases

2021 ◽  
Vol 4 (2) ◽  
pp. e000196
Author(s):  
Yue Wu ◽  
Xiaosi Jin ◽  
Yuhao Zhang ◽  
Jing Zheng ◽  
Rulai Yang
Keyword(s):  
Congenital Heart ◽  
Heart Diseases ◽  
Gene Mutations ◽  
Morbidity And Mortality ◽  
Molecular Medicine ◽  
Epigenetic Mechanisms ◽  
Epigenetic Factors ◽  
Near Future

Congenital heart disease (CHD) is the most common of congenital cardiovascular malformations associated with birth defects, and it results in significant morbidity and mortality worldwide. The classification of CHD is still elusive owing to the complex pathogenesis of CHD. Advances in molecular medicine have revealed the genetic basis of some heart anomalies. Genes associated with CHD might be modulated by various epigenetic factors. Thus, the genetic and epigenetic factors are gradually accepted as important triggers in the pathogenesis of CHD. However, few literatures have comprehensively elaborated the genetic and epigenetic mechanisms of CHD. This review focuses on the etiology of CHD from genetics and epigenetics to discuss the role of these factors in the development of CHD. The interactions between genetic and epigenetic in the pathogenesis of CHD are also elaborated. Chromosome abnormalities and gene mutations in genetics, and DNA methylations, histone modifications and on-coding RNAs in epigenetics are summarized in detail. We hope the summative knowledge of these etiologies may be useful for improved diagnosis and further elucidation of CHD so that morbidity and mortality of children with CHD can be reduced in the near future.

scholarly journals The Role of BMP Signaling in Osteoclast Regulation

2021 ◽  
Vol 9 (3) ◽  
pp. 24
Author(s):  
Brian Heubel ◽  
Anja Nohe
Keyword(s):  
Bone Formation ◽  
Bone Morphogenetic Proteins ◽  
Bone Diseases ◽  
Bmp Signaling ◽  
Bone Homeostasis ◽  
Direct Stimulation ◽  
Federal Drug Administration ◽  
Bmp Pathway ◽  
Stimulation Of

The osteogenic effects of Bone Morphogenetic Proteins (BMPs) were delineated in 1965 when Urist et al. showed that BMPs could induce ectopic bone formation. In subsequent decades, the effects of BMPs on bone formation and maintenance were established. BMPs induce proliferation in osteoprogenitor cells and increase mineralization activity in osteoblasts. The role of BMPs in bone homeostasis and repair led to the approval of BMP2 by the Federal Drug Administration (FDA) for anterior lumbar interbody fusion (ALIF) to increase the bone formation in the treated area. However, the use of BMP2 for treatment of degenerative bone diseases such as osteoporosis is still uncertain as patients treated with BMP2 results in the stimulation of not only osteoblast mineralization, but also osteoclast absorption, leading to early bone graft subsidence. The increase in absorption activity is the result of direct stimulation of osteoclasts by BMP2 working synergistically with the RANK signaling pathway. The dual effect of BMPs on bone resorption and mineralization highlights the essential role of BMP-signaling in bone homeostasis, making it a putative therapeutic target for diseases like osteoporosis. Before the BMP pathway can be utilized in the treatment of osteoporosis a better understanding of how BMP-signaling regulates osteoclasts must be established.

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