chondroblasts
Dotaz
Zobrazit nápovědu
BACKGROUND: Autophagy is classified as a form of programmed cell death. Nevertheless, besides the death-inducing function, autophagy enables removal of damaged organelles, energy savings, and thus cell survival. This applies in particular to cells with poor renewal capabilities, such as chondroblasts. Autophagy is regulated by a complex molecular network, including proteases and their substrates. In autopodium, autophagy-related proteases have been examined particularly within the context of the elimination of the interdigital tissue. However, the death-inducing effects of their expression/activation have not been specified yet. This work focuses on autophagy-associated proteases (cathepsins, matrix metalloproteinases, and caspases) in development of phalangeal cartilage of the mouse autopodium. METHODS: PCR Array, Real-time PCR, and immunohistochemistry were used to follow the expression of autophagy-associated genes in vivo at two developmental stages prenatal/embryonic (E)12 vs. E14. Real-time PCR was then applied to investigate the influence of rapamycin (an inducer of autophagy) on the expression of autophagy-associated proteases in chondroblasts in vitro using micromass culture. RESULTS: Several proteases showed increased expression levels during the transition of pre-chondrogenic cells into chondroblasts in vivo. The most significant increases were observed for Ctsb (fold regulation 2.22), Ctsd (fold regulation 2.37), Ctss (fold regulation 2.92), Mmp9 (up to 445%), and Casp8 (up to 250%). The transition was associated also with the high expression of crucial autophagic inducers, such as Atgs. The in vitro treatment of chondroblasts by rapamycin showed significantly decreased expression of cathepsins, a mild increase in expression of metalloproteinases, and no effect in caspase expression. CONCLUSIONS: The present data provide a screening of autophagy-associated proteases accompanying the formation of cartilage in vivo and specify their expression under rapamycin treatment in vitro. Notably, the selected proteases are assigned to osteoarthritis, therefore their regulation might be used in clinically oriented studies.
- MeSH
- apoptóza MeSH
- autofagie MeSH
- chondrocyty * MeSH
- chondrogeneze MeSH
- myši MeSH
- proteasy * MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
OBJECTIVE: The knowledge about functions of caspases, usually associated with cell death and inflammation, keeps expanding also regarding cartilage. Active caspases are present in the growth plate, and caspase inhibition in limb-derived chondroblasts altered the expression of osteogenesis-related genes. Caspase inhibitors were reported to reduce the severity of cartilage lesions in osteoarthritis (OA), and caspase-3 might represent a promising biomarker for OA prognosis. The objective of this investigation was to decipher the transcriptomic regulation of caspase inhibition in chondrogenic cells. DESIGN: Limb-derived chondroblasts were cultured in the presence of 2 different inhibitors: Z-VAD-FMK (FMK) and Q-VD-OPH (OPH). A whole transcriptome RNA sequencing was performed as the key analysis. RESULTS: The analysis revealed a statistically significant increase in the expression of 252 genes in the FMK samples and 163 genes in the OPH samples compared with controls. Conversely, there was a significant decrease in the expression of 290 genes in the FMK group and 188 in the OPH group. Among the top up- and downregulated genes (more than 10 times changed), almost half of them were associated with OA. Both inhibitors displayed the highest upregulation of the inflammatory chemokine Ccl5, the most downregulated gene was the one for mannose receptors Mrc1. CONCLUSIONS: The obtained datasets pointed to a significant impact of caspase inhibition on the expression of several chondro-/osteogenesis-related markers in an in vitro model of endochondral ossification. Notably, the list of these genes included some encoding for factors associated with cartilage/bone pathologies such as OA.
Primární řasinka je senzorická, solitární, nepohyblivá, mikrotubulární struktura, která v klidové části buněčného cyklu vyrůstá na povrch většiny lidských buněk, včetně kmenových buněk mezenchymu, osteoblastů, osteocytů, chondroblastů, chondrocytů, fibroblastů a fibrocytů. Primární řasinky se vyskytují i na povrchu chondrocytů osteoartrotické chrupavky a buněk benigních i maligních nádorů pojivové tkáně včetně enchondromu, osteochondromu, osteosarkomu, chondrosarkomu a Ewingova sarkomu kosti. Bazálním tělískem primární řasinky je mateřský centriol. Tématem tohoto přehledového sdělení jsou současné poznatky o primárních řasinkách buněk pojivové tkáně.
The primary cilium is a sensory, solitary, non-motile microtubule-based structure protruding in the quiescent phase of the cell cycle from the surface of the majority of human cells, including mesenchymal stem cells, osteoblasts, osteocytes, chondroblasts, chondrocytes, fibroblasts, fibrocytes, chondrocytes of osteoarthritic cartillage, tumor cells of benign and malignant tumors of connective tissue, including enchondroma, osteochondroma, osteosarcoma, chondrosarcoma and Ewing bone sarcoma. Primary cilium is formed from the mother centriole. The aim of this paper is to provide a review of the current knowledge on the primary cilia in connective tissue cells.
- Klíčová slova
- epifyzodiafyzární ploténka, kostní nádory,
- MeSH
- buňky pojivové tkáně * MeSH
- chondrocyty metabolismus MeSH
- cilie * fyziologie metabolismus MeSH
- lidé MeSH
- nádory kostí etiologie metabolismus MeSH
- osteoartróza etiologie metabolismus MeSH
- osteochondrom etiologie metabolismus MeSH
- růstová ploténka fyziologie MeSH
- sarkom etiologie metabolismus MeSH
- vývoj kostí MeSH
- Check Tag
- lidé MeSH
- Publikační typ
- práce podpořená grantem MeSH
- přehledy MeSH
Popisujeme prípad postradiačnej dediferenciácie meningoteliálneho meningeómu do chondroblastického osteosarkómu. Nádor vznikol u 61-ročného muža sedem rokov po adjuvantnom stereotaktickom ožiarení recidivujúceho meningeómu. Histologicky bol zachytený plynulý prechod z atypického meningeómu do klasického chondroblastického osteosarkómu. Pacient zomrel tri týždne po operácii, bez ďalšej onkologickej liečby. Podľa našich vedomostí ide iba o druhý popísaný prípad postradiačnej dediferenciácie meningeómu do osteosarkómu.
We report a case of post-radiation dedifferentiation of meningothelial meningioma into chondroblastic osteosarcoma. The tumor developed in a 61-year-old man, seven years after adjuvant stereotactical radiotherapy of recurring meningioma. Histologically, there was a continuous transition from atypical meningioma into chondroblastic osteosarcoma. The patient died three weeks after the surgery, without additional oncological treatment. To our knowledge, this case represents only the second reported case of post-radiation dedifferentiation of meningioma into osteosarcoma.
- MeSH
- adjuvantní radioterapie metody škodlivé účinky využití MeSH
- dediferenciace buněk účinky záření MeSH
- dospělí MeSH
- histologie MeSH
- imunohistochemie metody využití MeSH
- lidé MeSH
- meningeom diagnóza etiologie patologie MeSH
- neurochirurgické výkony metody využití MeSH
- osteosarkom diagnóza etiologie patologie MeSH
- počítačová rentgenová tomografie metody využití MeSH
- radiační onkologie metody MeSH
- Check Tag
- dospělí MeSH
- lidé MeSH
- mužské pohlaví MeSH
- Publikační typ
- kazuistiky MeSH
- MeSH
- chondrocyty metabolismus MeSH
- odontoblasty fyziologie MeSH
- osteoartróza patofyziologie MeSH
- Publikační typ
- kongresy MeSH
- MeSH
- chondrocyty fyziologie patologie MeSH
- kloubní chrupavka fyziologie patofyziologie MeSH
- osteoartróza patofyziologie MeSH
- Publikační typ
- kongresy MeSH
