Osteoporóza (OP) je systémové metabolické onemocnění charakterizované sníženým obsahem kostní hmoty a narušením mikroarchitektury kosti, což je příčinou zvýšené fragility kosti, a tím zvýšeného rizika zlomenin již při minimálním traumatu. Cílem léčby osteoporózy je restituce prořídlé kostní tkáně. Konečným a hlavním cílem je prevence zlomenin. Podle toho je možno také posuzovat účinnost léčby. Časnějším, nepřímým ukazatelem úspěšnosti léčby je zvýšení kostní denzity, nebo alespoň zpomalení jejího úbytku na fyziologickou hranici. Sklerostin je protein, který je u lidí kódován genem SOST. Sklerostin je produkován především osteocyty, má antianabolické účinky na novotvorbu kostí. Romosozumab je humanizovaná monoklonální protilátka IgG2 proti sklerostinu. Vývoj protilátky proti sklerostinu se jevil ideálním k ovlivnění novotvorby kosti právě pro téměř výhradní expresi genu SOST v kosti. Romosozumab se ukázal jako mimořádně účinný při zvyšování denzity kostního minerálu (BMD), modulaci markerů kostního obratu a redukci rizika fraktur. Při léčbě romosozumabem dochází k rychlému a účinnému snížení rizika zlomenin u postmenopauzálních žen s osteoporózou. Dvojí mechanizmus účinku činí z romosozumabu jedinečnou a účinnou možnost léčby osteoporózy, zejména v případech, v nichž je žádoucí rychlé navýšení denzity kostí. Významné snížení rizika zlomenin představuje podstatný klinický přínos.
Osteoporosis (OP) is a systemic metabolic disease characterized by reduced bone mass and disturbed bone microarchitecture, which causes increased bone fragility and thus increased risk of fractures even with minimal trauma. The goal of osteoporosis treatment is restitution of thinned bone tissue. The ultimate and main goal is fracture prevention. The effectiveness of treatment can also be judged accordingly. An early, indirect indicator of the success of treatment is an increase in bone density, or at least a slowing of bone loss to the physiological limit. Sclerostin is a protein that in humans is encoded by the SOST gene. Sclerostin is produced mainly by osteocytes and has antianabolic effects on bone formation. Romosozumab is a humanized IgG2 monoclonal antibody against sclerostin. The development of an antibody against sclerostin seemed ideal to affect bone formation precisely because of the almost exclusive expression of the SOST gene in bone. Romosozumab has proven to be extremely effective in increasing bone mineral density (BMD), modulating markers of bone turnover and reducing fracture risk. Treatment with romosozumab results in a rapid and effective reduction in fracture risk in postmenopausal women with osteoporosis. The dual mechanism of action makes romosozumab a unique and effective treatment option for osteoporosis, particularly in cases where rapid increases in bone density are desired. The significant reduction in fracture risk represents a substantial clinical benefit.
- Keywords
- romosozumab,
- MeSH
- Bone Density Conservation Agents therapeutic use MeSH
- Clinical Trials as Topic MeSH
- Cortical Bone drug effects ultrastructure MeSH
- Bone Density drug effects MeSH
- Humans MeSH
- Antibodies, Monoclonal * therapeutic use MeSH
- Drug-Related Side Effects and Adverse Reactions MeSH
- Osteoporotic Fractures prevention & control MeSH
- Osteoporosis * diagnosis drug therapy prevention & control MeSH
- Bone Remodeling drug effects MeSH
- Check Tag
- Humans MeSH
- Publication type
- Chart MeSH
- Review MeSH
INTRODUCTION: Fibroblast growth factor 20 (Fgf20), a member of the Fgf9 subfamily, was identified as an important regulator of bone differentiation and homeostasis processes. However, the role of Fgf20 in bone physiology has not been approached yet. Here we present a comprehensive bone phenotype analysis of mice with functional ablation of Fgf20. METHODS: The study conducts an extensive analysis of Fgf20 knockout mice compared to controls, incorporating microCT scanning, volumetric analysis, Fgf9 subfamily expression and stimulation experiment and histological evaluation. RESULTS: The bone phenotype could be detected especially in the area of the lumbar and caudal part of the spine and in fingers. Regarding the spine, Fgf20-/- mice exhibited adhesions of the transverse process of the sixth lumbar vertebra to the pelvis as well as malformations in the distal part of their tails. Preaxial polydactyly and polysyndactyly in varying degrees of severity were also detected. High resolution microCT analysis of distal femurs and the fourth lumbar vertebra showed significant differences in structure and mineralization in both cortical and trabecular bone. These findings were histologically validated and may be associated with the expression of Fgf20 in chondrocytes and their progenitors. Moreover, histological sections demonstrated increased bone tissue formation, disruption of Fgf20-/- femur cartilage, and cellular-level alterations, particularly in osteoclasts. We also observed molar dysmorphology, including root taurodontism, and described variations in mineralization and dentin thickness. DISCUSSION: Our analysis provides evidence that Fgf20, together with other members of the Fgf9 subfamily, plays a crucial regulatory role in skeletal development and bone homeostasis.
- MeSH
- Phenotype MeSH
- Fibroblast Growth Factors * metabolism genetics MeSH
- Calcification, Physiologic MeSH
- Bone and Bones metabolism pathology diagnostic imaging abnormalities MeSH
- Mice, Inbred C57BL MeSH
- Mice, Knockout * MeSH
- Mice MeSH
- Osteogenesis MeSH
- X-Ray Microtomography MeSH
- Animals MeSH
- Check Tag
- Male MeSH
- Mice MeSH
- Female MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
Three-dimensional (3D) cell cultures are to date the gold standard in biomedical research fields due to their enhanced biological functions compared to conventional two-dimensional (2D) cultures. 3D cell spheroids, as well as organoids, are better suited to replicate tissue functions, which enables their use both as in vitro models for basic research and toxicology, as well as building blocks used in tissue/organ biofabrication approaches. Culturing 3D spheroids from bone-derived cells is an emerging technology for both disease modelling and drug screening applications. Bone tissue models are mainly limited by the implementation of sophisticated devices and procedures that can foster a tissue-specific 3D cell microenvironment along with a dynamic cultivation regime. In this study, we consequently developed, optimized and characterized an advanced perfused microfluidic platform to improve the reliability of 3D bone cell cultivation and to enhance aspects of bone tissue maturation in vitro. Moreover, biomechanical stimulation generated by fluid flow inside the arrayed chamber, was used to mimic a more dynamic cell environment emulating a highly vascularized bone we expected to improve the osteogenic 3D microenvironment in the developed multifunctional spheroid-array platform. The optimized 3D cell culture protocols in our murine bone-on-a-chip spheroid model exhibited increased mineralization and viability compared to static conditions. As a proof-of-concept, we successfully confirmed on the beneficial effects of a dynamic culture environment on osteogenesis and used our platform for analysis of bone-derived spheroids produced from primary human pre-osteoblasts. To conclude, the newly developed system represents a powerful tool for studying human bone patho/physiology in vitro under more relevant and dynamic culture conditions converging the advantages of microfluidic platforms with multi-spheroid array technologies.
- Publication type
- Journal Article MeSH
Stopové prvky jsou v lidském těle součástí řady důležitých funkcí. Svůj nepochybný význam mají i pro vývoj skeletu od fetálního období s podílem na novotvorbě kosti, a v dospělosti pak v udržení její integrity. Některé stopové prvky mají na kost efekt protektivní (zinek), jiné naopak toxický (kadmium, chrom, kobalt). Měření koncentrací stopových prvků v tělních tekutinách (krev a moč) a ve tkáních (vlasy a kost) umožní identifikovat jedince ohrožené osteoporotickými frakturami v důsledku nutričního deficitu. Článek podává přehled součas- ných znalostí o významu stopových prvků pro fyziologii skeletu.
Trace elements are involved in a number of important functions in the human body. They are of undoubted importance for the development of the skeleton from the foetal period onwards, contributing to new bone formation, and in adulthood to the maintenance of its integrity. Some trace elements have a protective effect on the bone (zinc), others have a toxic effect (cadmium, chromium, cobalt). Measurement of trace element concentrations in body fluids (blood and urine) and tissues (hair and bone) will allow identification of individuals at risk of osteoporotic fractures due to nutritional deficiencies. This article provides current knowledge on the importance of trace elements for skeletal physiology.
- MeSH
- Skeleton * physiology growth & development MeSH
- Humans MeSH
- Nutritional Requirements MeSH
- Trace Elements * blood metabolism urine deficiency toxicity MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Mineralized tissues, such as bones or teeth, are essential structures of all vertebrates. They enable rapid movement, protection, and food processing, in addition to providing physiological functions. Although the development, regeneration, and pathogenesis of teeth and bones have been intensely studied, there is currently no tool to accurately follow the dynamics of growth and healing of these vital tissues in space and time. Here, we present the BEE-ST (Bones and tEEth Spatio-Temporal growth monitoring) approach, which allows precise quantification of development, regeneration, remodeling, and healing in any type of calcified tissue across different species. Using mouse teeth as model the turnover rate of continuously growing incisors was quantified, and role of hard/soft diet on molar root growth was shown. Furthermore, the dynamics of bones and teeth growth in lizards, frogs, birds, and zebrafish was uncovered. This approach represents an effective, highly reproducible, and versatile tool that opens up diverse possibilities in developmental biology, bone and tooth healing, tissue engineering, and disease modeling.
- MeSH
- Zebrafish * MeSH
- Bone and Bones MeSH
- Mice MeSH
- Bone Development MeSH
- Tooth Root MeSH
- Tooth * physiology MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
The review presents an evaluation of the development of on-line, at-line and in-line sample treatment coupled with capillary and microchip electrophoresis over the last 10 years. In the first part, it describes different types of flow-gating interfaces (FGI) such as cross-FGI, coaxial-FGI, sheet-flow-FGI, and air-assisted-FGI and their fabrication using molding into polydimethylsiloxane and commercially available fittings. The second part deals with the coupling of capillary and microchip electrophoresis with microdialysis, solid-phase, liquid-phase, and membrane based extraction techniques. It mainly focuses on modern techniques such as extraction across supported liquid membrane, electroextraction, single drop microextraction, head space microextraction, and microdialysis with high spatial and temporal resolution. Finally, the design of sequential electrophoretic analysers and fabrication of SPE microcartridges with monolithic and molecularly imprinted polymeric sorbents are discussed. Applications include the monitoring of metabolites, neurotransmitters, peptides and proteins in body fluids and tissues to study processes in living organisms, as well as the monitoring of nutrients, minerals and waste compounds in food, natural and wastewater.
- MeSH
- Electrophoresis, Capillary methods MeSH
- Electrophoresis, Microchip * methods MeSH
- Microdialysis MeSH
- Publication type
- Journal Article MeSH
- Review MeSH
Matrix Gla protein (MGP) je cirkulující protein s nízkou molekulární hmotností, který působí jako přirozený inhibitor kalcifikace. Řadíme ho do skupiny proteinů označených jako vitamin K dependentní proteiny. Jeho hlavní funkcí je prevence ukládání vápníku do měkkých tkání. Pro správné fungování musí být MGP dostatečně karboxylován a fosforylován, což je proces, který vyžaduje vitamin K2 jako kofaktor gamma-glutamylkarboxylasy. Nedostatek vitaminu K se projevuje kardiovaskulárním onemocněním, nedostatečnou mineralizací kostní tkáně a vznikem kalcifikujících deposit v měkkých tkáních. Cílem práce bylo navržení metod pro sledování hladiny MGP a defosforylovaného nedostatečně karboxylovaného MGP (dp-uc MGP) za využití imunochemické detekce a aplikovat je na analýzu reálných pacientských vzorků pro použití v klinických laboratořích, kde by tyto markery mohly sloužit jako potencionální markery závažnosti kloubních onemocnění, kardiovaskulárních onemocnění a také jako markery vypovídající o stavu vitaminu K v organismu.
Matrix Gla protein (MGP) is a circulating protein with a low molecular weight that acts as a natural inhibitor of calcification. It belongs to the group of vitamin K‐dependent proteins. For its proper function, MGP must undergo vitamin K-dependent carboxylation and phosphorylation. Its main function is the prevention of soft-tissue calcification. It requires vitamin K2 as a cofactor for gamma glutamyl carboxylase. Vitamin K insufficiency is manifested by cardiovascular diseases, insufficient mineralization of bone tissue and the formation of calcifying deposits in soft tissues. The aim of this study was to design methods for monitoring the levels of MGP and dp-uc MGP by using immunochemical detection and to apply them to the analysis of real samples for use in clinical laboratories. These markers could serve as potential markers of the severity of joint diseases, cardiovascular diseases and also as markers indicating the status of vitamin K in organism.
Úvod a cíl: Mimojícnový reflux (EER) je zpětný tok žaludečních šťáv (nejčastěji kyselých) nad úroveň horního jícnového svěrače (tím se liší od gastroezofageálního refluxu). Příznaky mimojícnového refluxu jsou nespecifické, různé intenzity a závisí na lokalizaci patologického působení refluxátu. V případě působení refluxátu na zubní tkáň může EER přispívat ke vzniku zubních erozí. Vedle refluxátu jsou zvažovány i další faktory, jako je složení slin a mikrobiom ústní dutiny. V posledních letech došlo k významnému posunu v chápání mimojícnového refluxu, zejména patogeneze a z toho vyplývajících důsledků pro diagnostiku a léčbu. Cílem článku je informovat o EER a podat přehled o současných možnostech diagnostiky a jeho léčby a také shrnout výsledky nedávných metaanalýz týkajících se role EER při vzniku zubních erozí. Metodika: Podkladem pro článek byly odborné publikace získané v databázích PubMed, Cochrane Library a Scopus z let 2002–2022. Publikace se vyhledávaly pomocí kombinace klíčových slov v anglickém i českém jazyce: mimojícnový reflux, gastroezofageální reflux, zubní eroze. Celkem bylo analyzováno 21 studií pojednávajících o souvislosti mezi refluxem a zubními erozemi prostřednictvím přehledových, klinických prospektivních a retrospektivních studií a metaanalýz. Zahrnuté studie byly provedeny u dospělé populace a informace o gastroezofageálním refluxu ve vztahu ke vzniku zubních erozí byly využity jen za předpokladu jeho diagnostiky multikanálovým intraluminálním monitorováním pH impedance. V první části článku je prezentován současný pohled na patofyziologii, diagnostiku a léčbu EER. Druhá část shrnuje poznatky o dentálních erozích. Ve třetí části jsou prezentovány studie zabývající se vlivem EER na zubní eroze. Výsledky: Získané informace svědčí o vyšší prevalenci dentálních erozí u pacientů s EER v porovnání se zdravou populací. Důvodem je, že kyseliny jak exogenního, tak endogenního původu hrají důležitou roli v rozpouštění minerálů skloviny, což ve výsledku vede ke vzniku zubních erozí. Na základě analyzovaných studií nelze v současnosti považovat vztah mezi refluxem a vznikem zubních erozí za kauzální, a to zejména z důvodu nízké kvality studií. Autoři doporučují provádění dalších studií, ve kterých by byl vztah mezi EER a zubními erozemi dále zkoumán. Závěr: Na základě dosavadních poznatků lze předpokládat účast mimojícnového refluxu na rozvoji dentálních onemocnění. Možnou souvislost podporuje i fakt, že prevalence dentálních erozí v populaci s refluxem nebo prevalence refluxu v populaci s dentálními erozemi je ve srovnání se zdravou populací mnohem vyšší. V budoucnosti je potřeba dalších studií, které by zkoumaly kauzalitu mimojícnového refluxu při vzniku zubních erozí.
Introduction, aim: Extraesophageal reflux (EER) is the backflow of gastric fluids (most often acidic) above the level of the upper esophageal sphincter (it differs from gastroesophageal reflux). The symptoms of extraesophageal reflux are non-specific, of varying intensity and depend on the location of the pathological action of the refluxate. In the case of the effect of refluxate on the hard dental tissue, EER can contribute to the formation of dental erosions. In addition to refluxate, other factors such as the composition of saliva and the microbiome of the oral cavity are discussed. In recent years, there has been a significant shift in the understanding of extraesophageal reflux, especially the pathogenesis, and the resulting implications for diagnosis and treatment. The aim of the article is to inform about EER and give an overview of the current possibilities of diagnosis and its treatment, as well as to summarize the results of recent meta-analyses regarding the role of EER in the development of dental diseases. Methods: The basis for the presented article was professional publications obtained in the PubMed, Cochrane Library and Scopus databases from 2002 to 2022. Publications were searched using a combination of keywords in English and Czech languages: extraesophageal reflux, gastroesophageal reflux, dental erosion. A total of 21 studies discussing the association between reflux and dental erosions were analyzed through review, clinical prospective and retrospective studies and meta-analyses. The included studies were conducted in the adult population and information on gastroesophageal reflux in relation to the occurrence of dental erosions was used only if it was diagnosed by multichannel intraluminal pH impedance monitoring. The first part of the article presents a current view of the pathophysiology, diagnosis and treatment of EER. The second part summarizes knowledge about dental erosions. In the third part, studies dealing with the effect of EER on dental erosion are presented. Results: The obtained information indicates a higher prevalence of dental erosions in patients with EER compared to the healthy population. The reason is that acids of both exogenous and endogenous origins play an important role in dissolving enamel minerals, which ultimately leads to tooth erosion. Based on the analyzed studies, the relationship between reflux and the development of dental erosions cannot currently be considered causal, mainly due to the low quality of the studies. The authors recommend that further studies investigating the relationship between EER and dental damage should be conducted. Conclusions: Based on the findings, it can be assumed that extraesophageal reflux is involved in the development of dental diseases. A possible link is also supported by the fact that the prevalence of dental erosions in population with reflux or the prevalence of reflux in the population with dental erosions is much higher compared to the healthy population. In the future, however, further studies are needed to investigate the causality of extraesophageal reflux in the occurrence of dental erosions.
- MeSH
- Tooth Erosion * etiology MeSH
- Laryngopharyngeal Reflux * complications MeSH
- Humans MeSH
- Microbiota MeSH
- Saliva MeSH
- Mouth microbiology MeSH
- Check Tag
- Humans MeSH
- Publication type
- Review MeSH
Considerable amount of research has been focused on dentin mineralization, odontoblast differentiation, and their application in dental tissue engineering. However, very little is known about the differential role of functionally and spatially distinct types of dental epithelium during odontoblast development. Here we show morphological and functional differences in dentin located in the crown and roots of mouse molar and analogous parts of continuously growing incisors. Using a reporter (DSPP-cerulean/DMP1-cherry) mouse strain and mice with ectopic enamel (Spry2+/- ;Spry4-/- ), we show that the different microstructure of dentin is initiated in the very beginning of dentin matrix production and is maintained throughout the whole duration of dentin growth. This phenomenon is regulated by the different inductive role of the adjacent epithelium. Thus, based on the type of interacting epithelium, we introduce more generalized terms for two distinct types of dentins: cementum versus enamel-facing dentin. In the odontoblasts, which produce enamel-facing dentin, we identified uniquely expressed genes (Dkk1, Wisp1, and Sall1) that were either absent or downregulated in odontoblasts, which form cementum-facing dentin. This suggests the potential role of Wnt signalling on the dentin structure patterning. Finally, we show the distribution of calcium and magnesium composition in the two developmentally different types of dentins by utilizing spatial element composition analysis (LIBS). Therefore, variations in dentin inner structure and element composition are the outcome of different developmental history initiated from the very beginning of tooth development. Taken together, our results elucidate the different effects of dental epithelium, during crown and root formation on adjacent odontoblasts and the possible role of Wnt signalling which together results in formation of dentin of different quality. © 2021 The Authors. Journal of Bone and Mineral Research published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research (ASBMR).
- MeSH
- Cell Differentiation MeSH
- Dentin * MeSH
- Epithelium MeSH
- Extracellular Matrix Proteins genetics MeSH
- Mice MeSH
- Odontoblasts * MeSH
- Odontogenesis MeSH
- Incisor MeSH
- Animals MeSH
- Check Tag
- Mice MeSH
- Animals MeSH
- Publication type
- Journal Article MeSH
- Research Support, Non-U.S. Gov't MeSH
