As the dentition forms and becomes functional, the alveolar bone is remodelled. Metalloproteinases are known to contribute to this process, but new regulators are emerging and their contextualization is challenging. This applies to Myb, a transcription factor recently reported to be involved in bone development and regeneration. The regulatory effect of Myb on Mmps expression has mostly been investigated in tumorigenesis, where Myb impacted the expression of Mmp1, Mmp2, Mmp7, and Mmp9. The aim of this investigation was to evaluate the regulatory influence of the Myb on Mmps gene expression, impacting osteogenesis and mandibular bone formation. For that purpose, knock-out mouse model was used. Gene expression of bone-related Mmps and the key osteoblastic transcription factors Runx2 and Sp7 was analysed in Myb knock-out mice mandibles at the survival limit. Out of the metalloproteinases under study, Mmp13 was significantly downregulated. The impact of Myb on the expression of Mmp13 was confirmed by the overexpression of Myb in calvarial-derived cells causing upregulation of Mmp13. Expression of Mmp13 in the context of other Mmps during mandibular/alveolar bone development was followed in vivo along with Myb, Sp7 and Runx2. The most significant changes were observed in the expression of Mmp9 and Mmp13. These MMPs and MYB were further localized in situ by immunohistochemistry and were identified in pre/osteoblastic cells as well as in pre/osteocytes. In conclusion, these results provide a comprehensive insight into the expression dynamics of bone related Mmps during mandibular/alveolar bone formation and point to Myb as another potential regulator of Mmp13.

• Klíčová slova
• MYB transcription factor, development and remodelling, mandibular alveolar bone, metalloproteinases, osteogenesis,
• Publikační typ
• časopisecké články MeSH

The MYB gene codes for the c-Myb transcription factor maintaining proliferation of colon epithelial progenitors, thus controlling colon development and homeostasis. This gene is overexpressed in early phases of colorectal cancer (CRC) tumorigenesis. The aim of this study was to examine the expression of c-Myb in CRC tissue samples both at the messenger RNA (mRNA) and protein levels and to evaluate their associations with clinicopathological characteristics in a group of 108 CRC patients. Statistically significant negative association was found between the frequency of the c-Myb-positive tumor cells assessed by immunohistochemistry and the presence of distant metastases (p < 0.01) but not tumor differentiation, tumor stage, lymph node involvement, vascular invasion, tumor localization, age, and gender of the patients. Although the c-Myb protein level in the tumor tissue correlated with its mRNA level, no significant association between MYB mRNA and any clinicopathological characteristics was observed. We conclude that albeit overexpression of c-Myb is considered as an important factor contributing to early phases of CRC tumorigenesis, it may later have negative effect on tumor cell dissemination as observed recently in breast cancer as well. Further studies are required to explain the role of c-Myb during formation of CRC distant metastases.

• Klíčová slova
• Colorectal cancer, Immunohistochemistry, Metastases, c-Myb, mRNA,
• MeSH
• adenokarcinom genetika   sekundární   MeSH
• buněčná diferenciace MeSH
• dospělí MeSH
• down regulace MeSH
• geny myb * MeSH
• invazivní růst nádoru MeSH
• kolorektální nádory genetika   patologie   MeSH
• lidé středního věku MeSH
• lidé MeSH
• lymfatické metastázy MeSH
• messenger RNA biosyntéza   MeSH
• nádorové proteiny biosyntéza   genetika   MeSH
• protoonkogenní proteiny c-myb biosyntéza   genetika   MeSH
• regulace genové exprese u nádorů MeSH
• RNA nádorová biosyntéza   MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• senioři nad 80 let MeSH
• senioři MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• messenger RNA MeSH
• nádorové proteiny MeSH
• protoonkogenní proteiny c-myb MeSH
• RNA nádorová MeSH

Caspases, well-known players in apoptosis or inflammation, appear to have roles also in other processes such as cell differentiation. Caspase-3, in particular, was recently demonstrated to have non-apoptotic functions in osteogenesis. However, the molecular pathways involved are not yet known. Therefore, we used osteogenic PCR arrays to provide a comprehensive screening of possible interactions of caspases in general and specifically of caspase-3 in osteogenic networks. Embryonic micromass cultures derived from mouse forelimbs were established and pharmacological fluoromethylketone (FMK) inhibitors applied. Alterations were observed in expression of several genes after caspase inhibition (Bmp1, Bmp5, Bmp6, Col10a1, Col2a1, Comp, Egf, Fgfr2, Gli1, Igf1, Nog, Phex, Sox9, Spp1). The list suggests molecular interactions of caspases and osteogenic molecules and creates a background for further temporospatial and functional studies.

• Klíčová slova
• Caspase-3, Caspases, Chondrogenesis, Gene expression, Osteogenesis,
• MeSH
• apoptóza účinky léků   MeSH
• buněčná diferenciace účinky léků   MeSH
• chondrogeneze účinky léků   MeSH
• inhibitory kaspas aplikace a dávkování   MeSH
• kaspasa 3 genetika   metabolismus   MeSH
• mezenchymální kmenové buňky účinky léků   MeSH
• myši MeSH
• osteogeneze účinky léků   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• inhibitory kaspas MeSH
• kaspasa 3 MeSH