The role of peptides in bone healing and regeneration: A systematic review

Background: Bone tissue engineering and the research surrounding peptides has expanded significantly over the last few decades. Several peptides have been shown to support and stimulate the bone healing response and have been proposed as therapeutic vehicles for clinical use. The aim of this comprehensive review is to present the clinical and experimental studies analysing the potential role of peptides for bone healing and bone regeneration. Methods: A systematic review according to PRISMA guidelines was conducted. Articles presenting peptides capable of exerting an upregulatory effect on osteoprogenitor cells and bone healing were included in the study. Results: Based on the available literature, a significant amount of experimental in vitro and in vivo evidence exists. Several peptides were found to upregulate the bone healing response in experimental models and could act as potential candidates for future clinical applications. However, from the available peptides that reached the level of clinical trials, the presented results are limited. Conclusion: Further research is desirable to shed more light into the processes governing the osteoprogenitor cellular responses. With further advances in the field of biomimetic materials and scaffolds, new treatment modalities for bone repair will emerge

Vitamin D and Sphingolipids: Role in Bone and Neural System

1-Alpha,25-dihydroxyvitamin D3 (1,25(OH)2D3) is known to play an important physiological role on growth and differentiation in a variety of nonmalignant and malignant cell types through classical actions, mediated by its specific receptor (VDR), and nongenomic actions resulting in the activation of specific signalling pathways. Due to the broad distribution of Vitamin D Receptor (VDR) in many tissues and the ability of 1,25(OH)2D3 to regulate fundamental processes, such as cell proliferation and differentiation, this steroid hormone has been suggested in the treatment of different diseases, from cancer to neurodegenerative diseases. In fact, structural 1,25(OH)2D3 analogues, with weaker collateral effects, have recently entered in clinical trials. Other interesting molecules due to their pleiotropic actions are the bioactive sphingolipids (SLs), in particular ceramide (Cer) and sphingosine 1-phosphate (S1P). Cells maintain a dynamic balance of these metabolites since Cer and sphingoid bases mediate cell death, while S1P exerts mitogenic effects and promotes differentiation of several cell types including osteogenic and neural cells. The biological actions of 1,25(OH)2D3 and SLs, in particular S1P, share many common effectors, including calcium regulation, growth factor expression, inflammatory cytokines, etc., but whether they could act synergistically is still unknown and deserves further investigation

Novel bioactivities of phosvitin in bone formation, collagen synthesis and bio-mineralization

Thesis (MSD) --Boston University, Henry M. Goldman School of Dental Medicine, 2015 (Department of Periodontology).Includes bibliography: leaves 104-115.Egg yolk phosvitin is one of the most highly phosphorylated extracellular matrix proteins known in nature with unique physico-chemical properties deem ed to be critical during ex-vivo egg embryo development. We have utilized our unique live m ouse calvarial bone organ culture models under conditions which dissociates the two bone remodeling stages, viz., resorption by osteoclasts and formation by osteoblasts, to highlight important and to date unknown critical biological functions of egg phosvitin. In our resorption model live bone cultures were grown in the absence of ascorbate and were stimulated by parathyroid hormone (PTH) to undergo rapid osteoclast formation/differentiation with bone resorption. In this resorption model native phosvitin potently inhibited PTH-induced osteoclastic bone resorption with simultaneous new osteoid/bone formation in the absence of ascorbate (vitamin C). These surprising and critical observations were extended using the bone formation model in the absence o f ascorbate and in the presence of phosvitin which supported the above results. The results were corroborated by analyses for calcium release or uptake, tartrate-resistant acid phosphatase activity ... [TRUNCATED

MAGNETIC FIELD AND TISSUE ENGINEERING: IMPACT AND EFFECT ON CELL-MATERIAL INTERACTIONS.

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The role of vitamin K in osteoporosis

According to the World Health Organization (WHO), osteoporosis is a “progressive systemic skeletal disease characterized by low bone mass and microarchitectural deterioration of bone tissue, with a consequent increase in bone fragility and susceptibility to fracture." The consequences of these fractures can be serious, sometimes life-threatening; the economic costs of treating fractures are also considerable. Alternative methods of treating osteoporosis have been researched in recent decades, and vitamin K (VK) has been found to be a viable therapeutic. This dissertation investigates scientific evidence on the role of VK in osteoporosis. VK is a fat-soluble vitamin required for blood clotting. VK has two main structures: vitamin K1 (VK1) and vitamin K2 (VK2). Different absorption rates, tissue distribution, and bioavailability reflect structural differences between VK1 and VK2. Although they have structural differences, both function as co-factor for the γ-glutamyl carboxylase enzyme (GGCX) in the conversion of glutamic acid (Glu) residues into γ-carboxyglutamic acid (Gla) residues in vitamin K-dependent proteins (VKDPs), involved in hepatic and extrahepatic activity. VKDPs involved in bone metabolism include osteocalcin (OC), matrix G1a protein (MGP), Gla Rich Protein (GRP), Growth Arrest Specific Protein 6 (Gas6), and protein S. OC is the most abundant VKDP in bone. During bone mineralization, osteoblasts produce OC, which binds to calcium ions and hydroxyapatite crystals to modulate bone size and structure. According to studies, VK2, especially menaquinone-7, has more positive results than VK1 in terms of improving bone mineral density (BMD) and decreasing the risk of fractures. In addition, VK2 suppresses IKB phosphorylation and reduces NF-κB activation, resulting in a decrease in the generation of pro-inflammatory cytokines implicated in osteoporosis physiopathology. VK2 also acts as a ligand for the steroid and xenobiotic receptor (SXR) or pregnane X receptor (PXR), increasing the transcription of genes for extracellular matrix proteins to preserve bone structure.Segundo a Organização Mundial de Saúde (OMS), a osteoporose é uma "doença sistémica progressiva caracterizada por baixa massa óssea e deterioração microarquitectónica do tecido ósseo, com um consequente aumento da fragilidade óssea e da suscetibilidade à fratura". As consequências destas fraturas podem ser graves, por vezes com risco de vida; os custos económicos do tratamento das fraturas são também consideráveis. Métodos alternativos de tratamento da osteoporose têm sido pesquisados nas últimas décadas, e a vitamina K (VK) tem sido considerada uma terapêutica viável. Esta dissertação investiga provas científicas sobre o papel da VK na osteoporose. A VK é uma vitamina lipossolúvel necessária para a coagulação do sangue. A VK tem duas estruturas principais: vitamina K1 (VK1) e vitamina K2 (VK2). Diferentes taxas de absorção, distribuição dos tecidos e biodisponibilidade refletem diferenças estruturais entre VK1 e VK2. Embora tenham diferenças estruturais, ambas funcionam como cofator da enzima γ-glutamil carboxilase (GGCX) na conversão de resíduos de ácido glutâmico (Glu) em resíduos de γ-carboxiglutâmico (Gla) em proteínas dependentes de vitamina K (VKDPs), envolvidas em atividade hepática e extra-hepática. Os VKDPs envolvidos no metabolismo ósseo incluem osteocalcina (OC), Matrix G1a Protein (MGP), Gla Rich Protein (GRP), Growth Arrest Specific Protein 6 (Gas6), e proteína S. OC é o VKDP mais abundante em osso. Durante a mineralização óssea, os osteoblastos produzem OC que se liga aos iões de cálcio e cristais de hidroxiapatite para alterar tamanho e estrutura óssea. De acordo com estudos, VK2 especialmente menaquinona-7, tem resultados mais positivos do que VK1 em termos de melhoria da BMD e de diminuição do risco de fraturas. VK2 funciona como um cofator na atividade de GGCX. Além disso, VK2 suprime a fosforilação IKB e reduz a ativação de NF-κB, resultando numa diminuição da geração de citocinas pró-inflamatórias implicadas na fisiopatologia da osteoporose. VK2 atua também como um ligante para o recetor esteroide e xenobiótico (SXR) ou recetor X pregnante (PXR), aumentando a transcrição de genes das proteínas de matriz extracelular para preservar a estrutura óssea

Bone-like inducing grafts: in vivo and micro-CT analysis

L'abstract è presente nell'allegato / the abstract is in the attachmen