Treatment of gingival fibroblasts with PDL extracellular vesicles results in promotion of Wnt signalling pathway and osteogenic differentiation. PDL secretome shows selective wound healing and matrix remodelling which can have implications for future periodontal regenerative strategies.
- MeSH
- buněčná diferenciace MeSH
- extracelulární vezikuly * fyziologie MeSH
- fibroblasty fyziologie MeSH
- gingiva cytologie MeSH
- hojení ran fyziologie MeSH
- lidé MeSH
- osteogeneze fyziologie MeSH
- periodontální vaz * cytologie fyziologie MeSH
- regenerace * fyziologie MeSH
- signální dráha Wnt fyziologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
Extracellular vesicles can play an important role in the processes occurring after stem cell transplantation, preventing cell apoptosis, stimulating immunological processes, and promoting the synthesis of extracellular matrix. Human follicular fluid (FF) can be a source of a subpopulation of cells with mesenchymal stem cells (MSCs) properties. Moreover these subpopulations of FF cells can differentiate into osteoblasts. In presented studies flow cytometry of ovarian FF cells confirmed positive expression of MSCs markers such as: CD44, CD90, CD105, CD73 and negative expression of a hematopoietic marker: CD45. The CD90+, CD105+, CD45- cell subpopulation has been obtained during magnetic separation using appropriate antibodies conjugated with microbeads. The extracellular vesicles (EVs) secreted by the cells during osteodifferentiation process differed from those secreted by cells culture in the basal medium. Based on the previous and current electron microscopy research, changes in size, number, and shape would support the notion that released EVs could be crucial to the ovarian FF cell subpopulation differentiation process. Osteogenic differentiation has been confirmed via Alizarin red staining. Therefore, follicular fluid (FF) can be a new source of a cell subpopulation with MSC properties, with the cells capable of differentiating into the osteogenic lineage. EVs could play a key role as mediators in tissue regeneration, especially bone tissue regeneration.
- MeSH
- buněčná diferenciace * MeSH
- extracelulární vezikuly * ultrastruktura metabolismus MeSH
- folikulární tekutina * cytologie metabolismus MeSH
- kultivované buňky MeSH
- lidé MeSH
- mezenchymální kmenové buňky * cytologie metabolismus MeSH
- osteoblasty cytologie metabolismus MeSH
- osteogeneze * MeSH
- průtoková cytometrie MeSH
- Check Tag
- lidé MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
The etiology of bone loss in celiac disease (CeD) remains a clinical challenge, with uncertainties present such as the extent of involvement of malabsorption and inflammation-induced osteoresorption processes in development of osteopenia/osteoporosis (OPN/OP), or reasons for failure to achieve healthy bone mass (BMD) even after long-term gluten-free diet (GFD) treatment. This observational prospective study explores the in vitro osteoclastogenic potential of peripheral blood precursors originating from adult active (newly diagnosed and untreated) celiac disease patients (aCeD) and describes the longitudinal changes in osteoclastogenesis after long-term adherence to GFD. To find connections between in vitro observations and in vivo bone metabolism changes, serum levels of 25(OH)D3, PTH, bCTX, PINP, CRP, IL-6, RANKL and OPG were measured before and after GFD and levels of these markers were correlated with the rate of osteoclastogenesis in vitro. OPG and IL-6 showed associations with BMD and/or presence of OPN/OP. Patients after GFD (CeD-GFD) exhibited improved BMD and increased serum 25(OH)D3 levels, alongside reduced bCTX and PINP levels. Compared to healthy donors, aCeD osteoclast genesis in vitro was higher and, surprisingly, remained elevated even in CeD-GFD patients. Negative correlation was found between osteoclastogenesis rate and serum OPG in aCeD, while osteoclastogenesis rate positively correlated with PTH in CeD-GFD. These results highlight OPG as marker for risk of OPN/OP in CeD and suggest that improvement of BMD after GFD is a result of uncoupling between bone metabolism and osteoresorptive action of osteoclasts after GFD.
- MeSH
- bezlepková dieta * MeSH
- celiakie * dietoterapie metabolismus MeSH
- dospělí MeSH
- interleukin-6 * krev metabolismus MeSH
- kostní denzita MeSH
- lidé středního věku MeSH
- lidé MeSH
- osteogeneze MeSH
- osteoklasty metabolismus MeSH
- osteoporóza etiologie metabolismus MeSH
- osteoprotegerin * krev metabolismus MeSH
- prospektivní studie MeSH
- vitamin D krev aplikace a dávkování MeSH
- Check Tag
- dospělí MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
- pozorovací studie MeSH
OBJECTIVE: Insulin-sensitizing drugs, despite their broad use against type 2 diabetes, can adversely affect bone health, and the mechanisms underlying these side effects remain largely unclear. Here, we investigated the different metabolic effects of a series of thiazolidinediones, including rosiglitazone, pioglitazone, and the second-generation compound MSDC-0602K, on human mesenchymal stem cells (MSCs). METHODS: We developed 13C subcellular metabolomic tracer analysis measuring separate mitochondrial and cytosolic metabolite pools, lipidomic network-based isotopologue models, and bioorthogonal click chemistry, to demonstrate that MSDC-0602K differentially affected bone marrow-derived MSCs (BM-MSCs) and adipose tissue-derived MSCs (AT-MSCs). In BM-MSCs, MSDC-0602K promoted osteoblastic differentiation and suppressed adipogenesis. This effect was clearly distinct from that of the earlier drugs and that on AT-MSCs. RESULTS: Fluxomic data reveal unexpected differences between this drug's effect on MSCs and provide mechanistic insight into the pharmacologic inhibition of mitochondrial pyruvate carrier 1 (MPC). Our study demonstrates that MSDC-0602K retains the capacity to inhibit MPC, akin to rosiglitazone but unlike pioglitazone, enabling the utilization of alternative metabolic pathways. Notably, MSDC-0602K exhibits a limited lipogenic potential compared to both rosiglitazone and pioglitazone, each of which employs a distinct lipogenic strategy. CONCLUSIONS: These findings indicate that the new-generation drugs do not compromise bone structure, offering a safer alternative for treating insulin resistance. Moreover, these results highlight the ability of cell compartment-specific metabolite labeling by click reactions and tracer metabolomics analysis of complex lipids to discover molecular mechanisms within the intersection of carbohydrate and lipid metabolism.
- MeSH
- adipogeneze * účinky léků MeSH
- buněčná diferenciace účinky léků MeSH
- hypoglykemika farmakologie MeSH
- kultivované buňky MeSH
- lidé MeSH
- metabolomika MeSH
- mezenchymální kmenové buňky * účinky léků metabolismus MeSH
- osteogeneze * účinky léků MeSH
- pioglitazon farmakologie MeSH
- rosiglitazon farmakologie MeSH
- thiazolidindiony * farmakologie MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: The primary aim of this study was to assess the amount and long-term stability of orthodontically created bone in patients with agenesis of maxillary lateral incisors after canine distalization. The secondary aim was to explore the impact of patient age on the process of alveolar bone resorption. METHODS: A group of patients with agenesis of the maxillary permanent lateral incisor was examined at 4 time points: the beginning of orthodontic treatment (T1, n = 80), the end of treatment (T2, n = 80), 2-5 years after treatment (T3, n = 79), and 12-15 years after treatment (T4, n = 32). The width of the edentulous alveolar bone was measured from study casts at the level of the bone ridge (point A) and 5 mm apically from the alveolar ridge (point B). Alveolar ridge height was also recorded using panoramic radiographs at all time points. Paired t tests, 2-sample t tests, Friedman test with Bonferroni correction, Spearman`s correlation, and linear regression tests were used to analyze the data. RESULTS: The alveolar ridge width was reduced by an average of 0.44 mm at point A and 0.47 mm at point B during the 12-15 years after treatment (T2-T4) and by 0.21 mm and 0.19 mm during the last 10 years (T3-T4). The alveolar ridge height was reduced by 0.59 mm between T2 and T4 and by 0.05 mm between T3 and T4. All reductions in ridge width and height were statistically significant (P <0.05). However, no significant correlation was observed between patient age and changes in alveolar bone parameters (P >0.05). CONCLUSIONS: Although the reductions in alveolar ridge dimensions were statistically significant, the orthodontically created bone after canine distalization remained stable 12-15 years after treatment in both the horizontal and vertical dimensions. Patient age did not significantly influence alveolar bone changes.
- MeSH
- anodoncie * terapie diagnostické zobrazování MeSH
- čelist bezzubá MeSH
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- maxila * MeSH
- mladiství MeSH
- mladý dospělý MeSH
- následné studie MeSH
- osteogeneze fyziologie MeSH
- posun zubů * metody MeSH
- processus alveolaris * diagnostické zobrazování patologie abnormality MeSH
- rentgendiagnostika panoramatická MeSH
- resorpce alveolární kosti diagnostické zobrazování MeSH
- řezáky * abnormality diagnostické zobrazování MeSH
- věkové faktory MeSH
- Check Tag
- dítě MeSH
- dospělí MeSH
- lidé MeSH
- mladiství MeSH
- mladý dospělý MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Bone nonunion delays fracture end repair and is associated with inflammation. Although bone nonunion can be effectively repaired in clinical practice, many cases of failure. Studies have confirmed that BMP-2 and nHA/PA66 repaired bone defects successfully. There are few studies on the effects of the combined application of BMP-2 and NHA/PA66 on bone nonunion osteogenesis and inflammation. We aimed to investigate the expression level of inflammation-related genes in patients with bone nonunion and the effect of BMP-2-infected mesenchymal stem cells combined with nHA/PA66 on the level of inflammation in femur nonunion rats. We searched for a gene expression profile related to bone nonunion inflammation (GSE93138) in the GEO public database. Bone marrow mesenchymal stem cells (MSCs) of SD rats were cultured and passed through. We infected the third generation of MSCs with lentivirus carrying BMP-2 and induced the infected MSCs to bone orientation. We detected the expression level of BMP-2 by RT-PCR and the cell viability and alkaline phosphatase (ALP) activity by CCK8 and then analyzed the cell adhesion ability. Finally, the levels of related inflammatory factors, including C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha) and Erythrocyte Sedimentation Rate (ESR), were detected in nonunion rats. Our findings: The patients with nonunion had up-regulated expression of 26 differentially inflammatory genes. These genes are mainly enriched in innate immune response, extracellular region, calcium ion binding, Pantothenate and CoA biosynthesis pathways. The expression level of BMP-2 in the Lenti-BMP-2 group was higher (vs. empty lentivirus vector group: t=5.699; vs. uninfected group t=3.996). The cell activity of the MSCs + BMP-2 + nHA/PA66 group increased gradually. After being combined with nHA/PA66, MSCs transfected with BMP-2 spread all over the surface of nHA/PA66 and grew into the material pores. MSCs + BMP-2 + nHA/PA66 cells showed positive ALP staining, and the OD value of ALP was the highest. The levels of CRP, IL-6, TNF-alpha, and ESR in the MSCs + BMP-2 + nHA/PA66 group were lower than those in the MSCs and MSCs + nHA/PA66 group but higher than those in MSCs + BMP-2 group. The above comparisons were all P<0.05. The findings demonstrated that the expression level of inflammation-related genes increased in the patients with bone nonunion. The infection of MSCs by BMP-2 could promote the directed differentiation of MSCs into osteoblasts in the bone marrow of rats, enhance the cell adhesion ability and ALP activity, and reduce inflammation in rats with bone nonunion.
- MeSH
- dospělí MeSH
- femur metabolismus patologie MeSH
- fraktury femuru metabolismus genetika MeSH
- kostní morfogenetický protein 2 * metabolismus genetika MeSH
- krysa rodu rattus MeSH
- kultivované buňky MeSH
- lidé středního věku MeSH
- lidé MeSH
- mezenchymální kmenové buňky * metabolismus MeSH
- nezhojené fraktury * genetika metabolismus MeSH
- osteogeneze MeSH
- potkani Sprague-Dawley * MeSH
- transplantace mezenchymálních kmenových buněk * MeSH
- zánět * metabolismus genetika MeSH
- zvířata MeSH
- Check Tag
- dospělí MeSH
- krysa rodu rattus MeSH
- lidé středního věku MeSH
- lidé MeSH
- mužské pohlaví MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVES: This study evaluated maxillary growth and dental arch relationships at 5 and 10 years of age in patients with unilateral cleft lip and palate (UCLP) who underwent early cleft lip and palate surgery. METHODS: 28 patients with UCLP who underwent cleft lip surgery in neonatal age and cleft palate surgery at average age of 7 months without orthodontic treatment (intervention group) were measured for intercanine and intermolar distances and for dental arch length. These measurements were compared with those of 30 healthy participants in a control group. Dental arch relationships in the intervention group were evaluated by 5-YO index at 5 years and the GOSLON Yardstick score at 10 years of patients' age. RESULTS: Patients in the intervention group had significantly shorter mean intercanine distance and arch length than control patients at both 5 and 10 years of age (p<.001 for all). There were no significant differences in intermolar distance at both 5 (p = .945) and 10 years (p = .105) of patients' age. The average 5YO index increased from 2.46 to an average GOSLON 10-year score of 2.89 in intervention group. CONCLUSION: Intercanine distance and dental arch length of patients with UCLP are significantly reduced at 5 and 10 years after early cleft lip and palate surgeries compared to the healthy population. Dental arch relationships at 5 and 10 years of patients with UCLP show comparable outcomes to those reported by other cleft centers. CLINICAL SIGNIFICANCE: This study evaluates maxillary growth in UCLP patients 5 and 10 years of age who underwent early primary lip and palate surgery.
- MeSH
- dítě MeSH
- lidé MeSH
- maxila * chirurgie růst a vývoj MeSH
- maxilofaciální vývoj MeSH
- předškolní dítě MeSH
- průřezové studie MeSH
- rozštěp patra * chirurgie MeSH
- rozštěp rtu * chirurgie MeSH
- studie případů a kontrol MeSH
- zubní oblouk * růst a vývoj patologie chirurgie MeSH
- Check Tag
- dítě MeSH
- lidé MeSH
- mužské pohlaví MeSH
- předškolní dítě MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
BACKGROUND: Acanthopanax senticosus (Rupr. et Maxim.) is commonly used in Traditional Chinese Medicine. Syringin is a major ingredient of phenolic glycoside in Acanthopanax senticosus. OBJECTIVE: This study was performed to investigate whether Syringin could protect high glucose-induced bone marrow mesenchymal stem cells (BMSCs) injury, cell senescence, and osteoporosis by inhibiting JAK2/STAT3 signaling. METHODS: BMSCs isolated from both the tibia and femur of mice were induced for osteogenesis. The cell senescence was induced using the high glucose medium. The cells were treated with 10 and 100 μmol/l Syringin. Immunohistochemistry staining was performed to determine the β-galactosidase (SA-β-gal) levels in differentially treated BMSCs. MTT assay and flow cytometry analysis were also performed to assess cell viability and cell cycle. The level of ROS in cells with different treatment was measured by using flow cytometry with DCF-DA staining. Calcium deposition and mineralized matrices were detected with alizarin red and ALP staining, respectively. Osteogenesis related genes OCN, ALP, Runx2, and BMP-2 were detected by RT-PCR. Levels of senescence-related proteins including p53 and p21, as well as JAK2, p-JAK2, STAT3, and p-STAT3 were detected by Western blot analysis. RESULTS: Syringin treatment reversed the phenotypes of senescence caused by high glucose in BMSCs, including the arrest of G0/G1 cell cycle, enhanced SA-β-gal activity, and impaired cell growth. Syringin also decreased the elevated ROS production and the levels of p53, p21, and JAK2/STAT3 signaling activation. In addition, Syringin also enhanced the osteogenic potential determined by ARS and ALP staining, as well as increasing OCN, ALP, Runx2, and BMP-2 expressions. CONCLUSION: Syringin protects high glucose-induced BMSC injury, cell senescence, and osteoporosis by inhibiting JAK2/STAT3 signaling.
- MeSH
- fenylpropionáty farmakologie MeSH
- glukosa * metabolismus toxicita MeSH
- glukosidy * farmakologie MeSH
- Janus kinasa 2 * metabolismus MeSH
- mezenchymální kmenové buňky * účinky léků metabolismus MeSH
- myši MeSH
- osteogeneze * účinky léků MeSH
- osteoporóza * prevence a kontrola metabolismus chemicky indukované patologie farmakoterapie MeSH
- reaktivní formy kyslíku metabolismus MeSH
- signální transdukce * účinky léků MeSH
- stárnutí buněk * účinky léků MeSH
- transkripční faktor STAT3 * metabolismus MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
INTRODUCTION: The Hueter-Volkmann law (HVL) of the response of growth plate to compression load is a basic concept in orthopaedics. However, little is known about the origin of HVL and its history. MATERIALS AND METHODS: A literature search was performed in original publications and historical sources. RESULTS: An analysis of all Volkmann ́s and Hueter ́s texts has shown that none of their publications was based on experiments, but on the data in the literature and their own clinical observations. They did not deal at all with the effect of pressure on the growth plate and mentioned this structure only marginally. The authors coined the opinion that increased pressure retards and decreased pressure accelerates bone growth. Julius Wolff criticized the HVL and concentrated all his arguments in the book "The law of bone remodeling". According to him, increased pressure leads to bone formation, decreased pressure to its resorption. The Wolff-Volkmann dispute was addressed in the German literature by a number of authors. Walther Müller in his monograph "The normal and pathological physiology of the bone" criticized Wolff for his concept of interstitial bone growth. In Müller ́s view, HVL applies to the growing bone and Wolff confuses growth with hypertrophy of the mature bone. CONCLUSION: The circumstances of the emergence of HVL are inaccurately and incompletely described in the current literature, as they are mostly taken from secondary sources. HVL, as it is presented today, is not the original formulation, but the result of a long historical evolution.
- MeSH
- dějiny 19. století MeSH
- dějiny 20. století MeSH
- lidé MeSH
- ortopedie * dějiny MeSH
- remodelace kosti fyziologie MeSH
- růstová ploténka * fyziologie MeSH
- vývoj kostí fyziologie MeSH
- Check Tag
- dějiny 19. století MeSH
- dějiny 20. století MeSH
- lidé MeSH
- Publikační typ
- časopisecké články MeSH
- historické články MeSH
- přehledy 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
- fenotyp MeSH
- fibroblastové růstové faktory * metabolismus genetika MeSH
- fyziologická kalcifikace MeSH
- kosti a kostní tkáň metabolismus patologie diagnostické zobrazování abnormality MeSH
- myši inbrední C57BL MeSH
- myši knockoutované * MeSH
- myši MeSH
- osteogeneze MeSH
- rentgenová mikrotomografie MeSH
- zvířata MeSH
- Check Tag
- mužské pohlaví MeSH
- myši MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
