Tibial pseudarthrosis often features deficient bone formation, excessive bone resorption, and extensive pathological fibrosis, particularly in individuals with Neurofibromatosis type I (NF1). It was hypothesized that overactive NF1-Ras-JNK signalling may underlie the pathological fibrosis, and that this could be treated via a JNK antagonist. CC-930, a small molecule JNK inhibitor, was trialed in closed fractures in wild type mice CC-930 (25 mg/kg/twice daily) was dosed throughout fracture healing (D2–21) and during the latter stages of repair (D11–21). All fractures healed by D21, regardless of treatment, with some of the CC-930 (D11–21) treatment group showing early bridging. CC-930 (D11–21) was tested in an Nf1-null fracture model where Nf1 was inactivated by Ad-Cre virus injection in Nf1flox/flox mice; these mice also possessed a Cre-responsive tdTomato transgene. CC-930 resulted in a significant decrease in non-unions (93% vehicle vs. 64% CC-930, p < 0.01). Local treatment with the bone anabolic rhBMP-2 (10 μg) increased union and callus bone volume, but also increased the fibrotic tissue at the fracture site. Fractures treated with a combination of rhBMP-2 (10 μg) and CC-930 were all partially or fully bridged by D21 (p < 0.01 vs. vehicle) and there was a significant decrease in fibrosis vs. rhBMP-2 alone (p < 0.01). In untreated Nf1-null fractures, the tdTomato transgene was expressed in fibrous tissue at the fracture site, but not in the newly forming bone. These data suggest that JNK inhibition may be an effective therapeutic approach for reducing pathological fibrosis in NF1 tibial pseudarthrosis, however other adjunctive strategies may be required to augment bone formation.

• MeSH
• fraktury tibie farmakoterapie   MeSH
• hojení fraktur MeSH
• JNK mitogenem aktivované proteinkinasy antagonisté a inhibitory   MeSH
• kostní morfogenetický protein 2 aplikace a dávkování   farmakologie   MeSH
• modely nemocí na zvířatech MeSH
• myši inbrední C57BL MeSH
• neurofibromatóza 1 * komplikace   MeSH
• pseudoartróza diagnostické zobrazování   patologie   prevence a kontrola   MeSH
• Publikační typ
• práce podpořená grantem MeSH

The aim of this study was to analyze the association between BMP2 (rs1884302) and DLX3 (rs2278163) gene polymorphisms and dental caries in primary and permanent dentitions. A total of 914 subjects were genotyped by the TaqMan methods: 176 caries-free children (with Decayed/Missing/Filled Teeth, DMFT = 0), 542 patients with dental caries in permanent dentition (DMFT ≥1), 83 caries-free children with primary teeth (with decayed/missing/filled teeth, dmft = 0), and 113 children with early childhood caries (ECC, dmft ≥1). There were no significant differences in allele/genotype frequencies between patients with caries in permanent dentition/ECC and caries-free children or between patients with very low (DMFT = 0-2), low (DMFT = 3-5), moderate (DMFT = 6-8), or high (DMFT ≥9) caries experience. Variability in BMP2 and DLX3 was not associated with caries in the Czech population.

• MeSH
• alely MeSH
• dentice trvalá MeSH
• dítě MeSH
• DMF Index MeSH
• genetická predispozice k nemoci MeSH
• genotyp MeSH
• homeodoménové proteiny genetika   MeSH
• jednonukleotidový polymorfismus * MeSH
• kostní morfogenetický protein 2 genetika   MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• stupeň závažnosti nemoci MeSH
• transkripční faktory genetika   MeSH
• zubní kaz genetika   MeSH
• zuby mléčné MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

Endodontic treatment of immature permanent teeth with necrotic pulp poses several clinical challenges and is one of the most demanding interventions in endodontics. Recently, with new discoveries in the field of tissue engineering, novel treatment protocols have been established. The most promising treatment modality is revascularization, whose integral part is the exposure of collagen matrix and embedded growth factors. However, optimization of the treatment protocol requires a development of analytical procedures able to analyze growth factors directly on the sample surface. In this work, method based on surface-enhanced Raman spectroscopy (SERS) was developed to investigate the influence of the time of the medical treatment using EDTA on exposure and accessibility of the growth factors, namely TGF-ß1, BMP-2, and bFGF on the dentine surface. The nanotags, which consist of magnetic Fe3O4@Ag nanocomposite covalently functionalized by tagged antibodies (anti-TGF-ß1-Cy3, anti-BMP-2-Cy5, and anti-bFGF-Cy7), were employed as a SERS substrate. Each antibody was coupled with a unique label allowing us to perform a parallel analysis of all three growth factors within one analytical run. Developed methodology presents an interesting alternative to a fluorescence microscopy and in contrary allows evaluating a chemical composition and thus minimizing possible false-positive results. Graphical abstract.

• MeSH
• dentin chemie   MeSH
• fibroblastový růstový faktor 2 analýza   MeSH
• kavita zubní dřeně chemie   MeSH
• kostní morfogenetický protein 2 analýza   MeSH
• lidé MeSH
• nanokompozity chemie   MeSH
• oxid železnato-železitý chemie   MeSH
• Ramanova spektroskopie metody   MeSH
• stříbro chemie   MeSH
• transformující růstový faktor beta analýza   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH

The aim of this study was to analyze the association between BMP2 (rs1884302) and DLX3 (rs2278163) gene polymorphisms and dental caries in primary and permanent dentitions. A total of 914 subjects were genotyped by the TaqMan methods: 176 caries-free children (with Decayed/Missing/Filled Teeth, DMFT = 0), 542 patients with dental caries in permanent dentition (DMFT ≥1), 83 caries-free children with primary teeth (with decayed/missing/filled teeth, dmft = 0), and 113 children with early childhood caries (ECC, dmft ≥1). There were no significant differences in allele/genotype frequencies between patients with caries in permanent dentition/ECC and caries-free children or between patients with very low (DMFT = 0-2), low (DMFT = 3-5), moderate (DMFT = 6-8), or high (DMFT ≥9) caries experience. Variability in BMP2 and DLX3 was not associated with caries in the Czech population.

• MeSH
• alely MeSH
• dentice trvalá MeSH
• dítě MeSH
• DMF Index MeSH
• genetická predispozice k nemoci MeSH
• genotyp MeSH
• homeodoménové proteiny genetika   MeSH
• jednonukleotidový polymorfismus * MeSH
• kostní morfogenetický protein 2 genetika   MeSH
• lidé MeSH
• mladiství MeSH
• předškolní dítě MeSH
• stupeň závažnosti nemoci MeSH
• transkripční faktory genetika   MeSH
• zubní kaz genetika   MeSH
• zuby mléčné MeSH
• Check Tag
• dítě MeSH
• lidé MeSH
• mladiství MeSH
• mužské pohlaví MeSH
• předškolní dítě MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Česká republika MeSH

Our goal was to determine if venlafaxine has a negative effect on bone metabolism. Rats were divided into three groups. The sham-operated control group (SHAM), the control group after orchidectomy (ORX), and the experimental group after orchidectomy received venlafaxine (VEN ORX) in standard laboratory diet (SLD) for 12 weeks. Bone mineral content (BMC) was measured by dual energy X-ray absorptiometry (DXA). Bone marker concentrations of carboxy-terminal cross-linking telopeptide of type I collagen (CTX-I), osteoprotegerin (OPG), amino-terminal propeptide of procollagen type I (P1NP), bone alkaline phosphatase (BALP), sclerostin and bone morphogenetic protein 2 (BMP-2) were examined in bone homogenate. The femurs were used for biomechanical testing. Compared to the ORX group we found lower BMD in the diaphysis area of the femur in the VEN ORX group, suggesting a preferential effect on cortical bone. Of the bone metabolism markers, there was significant decrease (ORX control group versus VEN ORX experimental group) in BALP levels and increase in sclerostin and CTX-I levels, suggesting a decrease in osteoid synthesis and increased bone resorption. The results suggest that the prolonged use of venlafaxine may have a negative effect on bone metabolism. Further studies are warranted to establish whether venlafaxine may have a clinically significant adverse effect on bone.

• MeSH
• absorpční fotometrie MeSH
• alkalická fosfatasa metabolismus   MeSH
• bederní obratle účinky léků   radiografie   MeSH
• biologické markery metabolismus   MeSH
• biomechanika MeSH
• femur účinky léků   radiografie   MeSH
• genetické markery MeSH
• inhibitory zpětného vychytávání serotoninu a noradrenalinu toxicita   MeSH
• kolagen typu I metabolismus   MeSH
• kosti a kostní tkáň účinky léků   metabolismus   účinky záření   MeSH
• kostní denzita účinky léků   MeSH
• kostní morfogenetické proteiny metabolismus   MeSH
• kostní morfogenetický protein 2 metabolismus   MeSH
• lidé MeSH
• orchiektomie * MeSH
• osteoprotegerin metabolismus   MeSH
• peptidové fragmenty metabolismus   MeSH
• peptidy metabolismus   MeSH
• potkani Wistar MeSH
• prokolagen metabolismus   MeSH
• remodelace kosti účinky léků   MeSH
• tibie účinky léků   metabolismus   MeSH
• venlafaxin hydrochlorid toxicita   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Introduction: Ankylosing spondylitis (AS) is an inflammatory rheumatic disease characterized by the development of osteoproductive changes in the spine which could possibly result in ankylosis. Treatment with tumour necrosis factor alpha (TNFα) inhibitors has proved to be an important step forward in the treatment of this disease, but for the time being it is not clear whether it favourably influences radiographic progression of the disease. Vascular endothelial growth factor most probably plays a role in the development of osteoproductive changes and recently its predictive influence on radiographic progression has been demonstrated. Bone morphogenic protein 2 (BMP-2) participates in the regulation of bone proliferation and its increased serum level has been demonstrated in patients with advanced AS and correlated with the degree of radiographic changes. Aim: The study aims to evaluate the VEGF and BMP-2 levels in patients with ankylosing spondylitis and how these levels relate to the concurrent treatment with TNFα inhibitors. Methods: Sera were evaluated from patients at the Rheumatologic Clinic of the Hradec Králové Faculty Hospital who fulfilled the modified New York Criteria for AS (n = 55). In these patients, the parameters of the activity of the disease (BASDAI = Bath Ankylosing Spondylitis Disease Activity Index, CRP = C-reactive protein) and the concurrent therapy (TNFα inhibitors, n = 21, vs. non-anti TNFα, n = 34) were recorded. The levels of VEGF and BMP-2 were analyzed using the ELISA method. Results: In patients treated with TNFα inhibitors, a significantly lower VEGF level was found when compared to untreated patients (140.3 (109.4; 262.2) vs. 261 (172.4; 396.6) pg/ml; p = 0.02). No difference was found between BMP-2 levels in both groups (treated vs. untreated patients) (254.8 (2301; 267.3) vs. 261.1 (248.6; 273.5) pg/ml; p = 0.24). A correlation analysis did not reveal any relationship between VEG F and BMP-2 (r = 0.057; p = 0.68). Serum levels of VEGF correlated with serum levels of CRP (r = 0.56; p = 0.00001) and the BASDAI value (r = 0.33; p = 0.015). Conclusion: Significantly lower VEGF levels were found in patients treated with TNFα inhibitors versus the untreated patients. These findings are in harmony with some hitherto published analyses and may give evidence of a favourable effect of TNFα inhibitors on radiographic progression. Neither influence on the BMP-2 level by treatment with TNFα inhibitors nor correlation with VEGF levels was demonstrated.

• MeSH
• ankylózující spondylitida krev   farmakoterapie   MeSH
• C-reaktivní protein metabolismus   MeSH
• dospělí MeSH
• ELISA MeSH
• kostní morfogenetický protein 2 krev   MeSH
• lidé středního věku MeSH
• lidé MeSH
• progrese nemoci MeSH
• TNF-alfa antagonisté a inhibitory   MeSH
• vaskulární endoteliální růstový faktor A krev   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH

x

• MeSH
• časové faktory MeSH
• exprese genu MeSH
• fraktury femuru farmakoterapie   radiografie   MeSH
• hojení fraktur * účinky léků   MeSH
• kostní morfogenetické proteiny genetika   terapeutické užití   MeSH
• kostní morfogenetický protein 2 * aplikace a dávkování   genetika   MeSH
• kostní morfogenetický protein 4 genetika   MeSH
• kostní morfogenetický protein 6 genetika   MeSH
• kostní morfogenetický protein 7 genetika   MeSH
• kostní svalek MeSH
• krysa rodu rattus MeSH
• kvantitativní polymerázová řetězová reakce statistika a číselné údaje   MeSH
• messenger RNA MeSH
• mezibuněčné signální peptidy a proteiny genetika   MeSH
• osteogeneze účinky léků   MeSH
• potkani Sprague-Dawley MeSH
• regenerace kostí genetika   účinky léků   MeSH
• rekombinantní proteiny MeSH
• stanovení celkové genové exprese MeSH
• TNF-alfa genetika   MeSH
• uzavřené fraktury MeSH
• výzkum MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• ženské pohlaví MeSH
• zvířata MeSH

There is only limited data concerning the effect of the newer antiepileptic drugs on bone. The objective of this study was to determine the effect of topiramate (TPM) and lamotrigine (LTG) monotherapy on bone mineral density (BMD), mineral content (BMC), bone markers, body composition and bone mechanical strength in the orchidectomized (ORX) rat model. 24 orchidectomized Wistar rats were divided into control and test groups, 8 rats in each group. The control rats received standard laboratory diet (SLD) while rats in the test group were fed with SLD enriched with LTG or TPM for 12 weeks. Dual energy X-ray absorptiometry was used to measure bone mineral density. The concentrations of bone metabolism markers were assayed in bone homogenate. In addition, both femurs were measured and used for biomechanical testing. Compared to the control group, both test groups had significantly lower weight, fat mass, whole body and femur BMD, BMC and reduced mechanical strength of bone. All of these changes were more pronounced in rats exposed to LTG. In conclusion, both LTG and TPM significantly reduce BMD and body weight and impair mechanical strength of bone. A question arises as to the degree of dependence of the effect on the dose. Further studies are warranted to establish whether LTG and TPM may have a clinically significant effect on BMD exclusively in the model of gonadectomized rats, or whether the effect applies also in the model of gonadally intact animals, and in the respective human models.

• MeSH
• absorpční fotometrie MeSH
• alkalická fosfatasa metabolismus   MeSH
• antikonvulziva aplikace a dávkování   MeSH
• aplikace orální MeSH
• biomechanika účinky léků   MeSH
• ELISA MeSH
• fruktosa analogy a deriváty   farmakologie   MeSH
• kolagen typu I metabolismus   MeSH
• kosti a kostní tkáň účinky léků   metabolismus   MeSH
• kostní denzita účinky léků   MeSH
• kostní morfogenetický protein 2 metabolismus   MeSH
• krysa rodu rattus MeSH
• modely u zvířat MeSH
• neparametrická statistika MeSH
• orchiektomie MeSH
• osteoprotegerin krev   MeSH
• peptidové fragmenty metabolismus   MeSH
• peptidy metabolismus   MeSH
• potkani Wistar MeSH
• prokolagen metabolismus   MeSH
• složení těla účinky léků   MeSH
• tělesná hmotnost účinky léků   MeSH
• triaziny aplikace a dávkování   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

OBJECTIVE: To determine the effect of levetiracetam (LEV) Lon bone mineral density (BMD), mineral content (BMC), bone markers, body composition and bone mechanical strength in the orchidectomised (ORX) rat model. METHOD: 16 orchidectomised Wistar rats were divided into control and test groups, 8 rats in each group. The control rats received standard laboratory diet (SLD) while rats in the test group were fed with SLD enriched with LEV for 12 weeks. BMD was measured by dual energy X-ray absorptiometry at the whole body, lumbar spine and femur. Bone marker concentrations were examined of osteoprotegerin (OPG) and insulin-like growth factor 1 (IGF-1) in serum, and amino-terminal propeptide of procollagen type I (PINP), carboxy-terminal cross-linking telopeptide of type I collagen (CTX-I), bone alkaline phosphatase (ALPL), and bone morphogenetic protein 2 (BMP-2) in bone homogenate. The femurs were used for biomechanical testing. RESULTS: Compared to the control group we found lower fat mass, lower BMD in the area of the left femur, lower BMC in both femurs, a reduced concentration of OPG, and an increased concentration of CTX-I of borderline statistical significance (p=0.0661). Biomechanical parameters did not differ between groups. CONCLUSIONS: Significant loss of BMD or BMC was seen at the left and right femur area in the LEV group. Administration of LEV in the ORX-rat model significantly decreased levels of OPG (marker of bone formation) in serum and increased levels of CTX-I (marker of bone resorption) in bone homogenate, but results in this study did not reveal any change in biomechanical bone strength. Administration of LEV in the ORX-rat model may reduce adipose tissue. Further studies in animals and humans will be needed to confirm these findings.

• MeSH
• alkalická fosfatasa krev   MeSH
• biologické markery krev   MeSH
• kolagen typu I krev   MeSH
• kosti a kostní tkáň účinky léků   metabolismus   MeSH
• kostní denzita účinky léků   MeSH
• kostní morfogenetický protein 2 krev   MeSH
• krysa rodu rattus MeSH
• osteoprotegerin krev   MeSH
• piracetam analogy a deriváty   farmakologie   MeSH
• potkani Wistar MeSH
• složení těla účinky léků   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

AIM: Our study aimed to investigate the effect of amlodipine on bone metabolism in orchidectomized rats. METHODS: Eight-week-old rats were divided into three groups. The sham-operated control group (SHAM) and the control group after orchidectomy (ORX) received the standard laboratory diet (SLD). The experimental group after orchidectomy (ORX+AML) received SLD enriched with amlodipine for 12 weeks. Bone marker concentrations in serum of PINP, OPG and IGF-1, and the levels of CTX-I, BAP and BMP-2 in a bone homogenate were measured using enzyme-linked immunosorbent assay. Bone mineral density (BMD) was measured by dual energy X-ray absorptiometry. The femurs were used for biomechanical testing. RESULTS: Bone markers (CTX-I, BAP, BMP-2) in ORX were higher versus SHAM. In ORX+AML there was a decrease in PINP, CTX-I, BAP, BMP-2 and OPG versus ORX. IGF-1 was decreased in ORX versus SHAM. In ORX+AML it was increased versus ORX. In ORX, a decrease was demonstrated versus SHAM in BMD of the whole body, in the lumbar vertebrae and in both femurs. In ORX+AML there was an increase in BMD of the whole body versus ORX. Three-point bending test revealed a decrease in maximal load values in ORX versus SHAM. After amlodipine administration there was an increase in the left femur versus ORX. CONCLUSIONS: Amlodipine is capable of mitigating the negative effects of orchidectomy and could be a good prevention of osteoporosis.

• MeSH
• alkalická fosfatasa metabolismus   MeSH
• amlodipin farmakologie   terapeutické užití   MeSH
• biologické markery krev   MeSH
• biomechanika fyziologie   MeSH
• blokátory kalciových kanálů farmakologie   terapeutické užití   MeSH
• insulinu podobný růstový faktor I metabolismus   MeSH
• kolagen typu I metabolismus   MeSH
• kosti a kostní tkáň účinky léků   metabolismus   MeSH
• kostní denzita účinky léků   MeSH
• kostní morfogenetický protein 2 metabolismus   MeSH
• krysa rodu rattus MeSH
• modely nemocí na zvířatech MeSH
• orchiektomie škodlivé účinky   MeSH
• osteoporóza farmakoterapie   patofyziologie   prevence a kontrola   MeSH
• osteoprotegerin krev   MeSH
• peptidové fragmenty krev   MeSH
• potkani Wistar MeSH
• prokolagen krev   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH