Mammalian Meckel´s cartilage is a temporary structure associated with mandible development. Notably, its elimination is not executed by apoptosis, and autophagy was suggested as the major mechanism. Simultaneous reports point to pro-apoptotic caspases as novel participants in autophagic pathways in general. The aim of this research was to find out whether activation of pro-apoptotic caspases (-2, -3, -6, -7, -8 and -9) was associated with autophagy of the Meckel´s cartilage chondrocytes. Active caspases were examined in serial histological sections of mouse mandible using immunodetection and were correlated with incidence of autophagy based on Beclin-1 expression. Caspase-2 and caspase-8 were found in Beclin-1 positive regions, whereas caspase-3, -6, -7 and -9 were not present. Caspase-8 was further correlated with Fas/FasL and HIF-1alpha, potential triggers for its activation. Some Fas and FasL positivity was observed in the chondrocytes but caspase-8 activation was found also in FasL deficient cartilage. HIF-1alpha was abundantly present in the hypertrophic chondrocytes. Taken together, caspase-8 activation in the Meckel´s cartilage was demonstrated for the first time. Caspase-8 and caspase-2 were the only pro-apoptotic caspases detected in the Beclin-1 positive segment of the cartilage. Activation of caspase-8 appears FasL/Fas independent but may be switched on by HIF-1alpha.

• MeSH
• apoptóza fyziologie   MeSH
• autofagie fyziologie   MeSH
• kaspasy metabolismus   MeSH
• kloubní chrupavka cytologie   metabolismus   MeSH
• lidé MeSH
• mandibula cytologie   metabolismus   MeSH
• myši MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH

Caspases have functions particularly in apoptosis and inflammation. Increasing evidence indicates novel roles of these proteases in cell differentiation, including those involved in osteogenesis. This investigation provides a complex screening of osteogenic markers affected by pan caspase inhibition in micromass cultures derived from mouse forelimbs. PCR Array analysis showed significant alterations in expression of 49 osteogenic genes after 7 days of inhibition. The largest change was a decrease in CD36 expression, which was confirmed at organ level by caspase inhibition in cultured mouse ulnae followed by CD36 immunohistochemical analysis. So far, available data point to osteogenic potential of pro-apoptotic caspases. Therefore, the expression of pro-apoptotic caspases (-3, -6, -7, -8, -9) within the growth plate of mouse forelimbs at the stage where the individual zones are clearly apparent was studied. Caspase-9 was reported in the growth plate for the first time as well as caspase-6 and -7 in the resting zone, caspase-7 in the proliferation, and caspase-6 and -8 in the ossification zone. For all caspases, there was a gradient increase in activation toward the ossification zone. The distribution of staining varied significantly from that of apoptotic cells, and thus, the results further support non-apoptotic participation of caspases in osteogenesis.

• MeSH
• antigeny CD36 analýza   genetika   MeSH
• imunohistochemie MeSH
• inhibitory kaspas farmakologie   MeSH
• kaspasy metabolismus   MeSH
• kultivované buňky MeSH
• myši MeSH
• orgánové kultury - kultivační techniky MeSH
• osteogeneze * účinky léků   MeSH
• přední končetina růst a vývoj   metabolismus   MeSH
• vývojová regulace genové exprese účinky léků   MeSH
• zvířata MeSH
• Check Tag
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

• MeSH
• antioxidancia MeSH
• biochemická analýza krve MeSH
• dvojchroman draselný krev   škodlivé účinky   toxicita   MeSH
• glutathion analýza   účinky léků   MeSH
• glutathionperoxidasa analýza   účinky léků   MeSH
• glutathionreduktasa analýza   účinky léků   MeSH
• otrava patofyziologie   MeSH
• peroxidace lipidů účinky léků   MeSH
• Pleurotus * MeSH
• potkani Wistar fyziologie   krev   MeSH
• potravní doplňky škodlivé účinky   MeSH
• sloučeniny chromu * krev   škodlivé účinky   toxicita   MeSH
• statistika jako téma MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH