Department of Physiology, University of Veterinary Sciences Brno, Brno, Czech Republic; Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Brno, Czech Republic.
Institute of Animal Physiology and Genetics, Czech Academy of Sciences, Brno, Czech Republic.
Tissue Cell. 2024 Aug;89:102425. doi: 10.1016/j.tice.2024.102425. Epub 2024 Jun 1.
Caspase-11 is the murine homologue of human caspases-4 and -5 and is involved in mediating the inflammatory response. However, its functions are often confused and misinterpreted with the more important and better described caspase-1. Therefore, this study focused exclusively on the specific roles of caspase-11, both in cartilage formation and in the inflammatory environment. The presence of caspase-11 during mouse limb development and in chondrogenic cell cultures was investigated by immunofluorescence detection. Subsequently, the function of caspase-11 was downregulated and the affected molecules investigated. The expression analysis applied for osteo/chondrogenesis associated factors and inflammatory cytokines. Simultaneously, morphological appearance of the micromass cultures was evaluated. The results revealed that caspase-11 is physiologically present during cartilage development, but its inhibition under physiological conditions has no significant effect on chondrogenic differentiation. However, in an inflammatory environment, inhibition and downregulation of caspase-11 leads to reduced differentiation of cartilage nodules. Additionally, reduced expression of several genes including Col2a1 and Sp7 and conversely increased expression of Mmp9 were observed. In the cytokine expression panel, a significant decrease was found in molecules that, along with the inflammatory function, may also be involved in cartilage differentiation. The findings bring new information about caspase-11 in chondrogenesis and show that its downregulation under inflammatory conditions reduces cartilage formation.
Caspase-11 是人类 caspase-4 和 caspase-5 的鼠同源物，参与介导炎症反应。然而，其功能经常与更为重要和描述更为详尽的 caspase-1 相混淆和误解。因此，本研究专门关注 caspase-11 在软骨形成和炎症环境中的特定作用。通过免疫荧光检测研究了 caspase-11 在小鼠肢发育过程中和软骨细胞培养物中的存在情况。随后，下调 caspase-11 的功能并研究受影响的分子。对与成骨/软骨形成相关的因子和炎症细胞因子进行了表达分析。同时，评估了微团培养物的形态外观。结果表明，caspase-11 在软骨发育过程中生理性存在，但在生理条件下抑制其活性对软骨形成分化没有显著影响。然而，在炎症环境中，caspase-11 的抑制和下调导致软骨结节的分化减少。此外，观察到包括 Col2a1 和 Sp7 在内的几个基因的表达减少，而 Mmp9 的表达增加。在细胞因子表达谱中，发现与炎症功能相关的分子显著减少，这些分子可能也参与软骨分化。这些发现提供了关于 caspase-11 在软骨形成中的新信息，并表明其在炎症条件下的下调会减少软骨形成。
