Abstract
Caspases are evolutionary conserved proteases traditionally known as participating in apoptosis and inflammation but recently discovered also in association with other processes such as proliferation or differentiation. This investigation focuses on caspase-12, ranked among inflammatory caspases but displaying other, not yet defined functions. A screening analysis pointed to statistically significant (P < 0.001) increase in expression of caspase-12 in a decisive period of mandibular bone formation when the original mesenchymal condensation turns into vascularized bone tissue. Immunofluorescence analysis confirmed the presence of caspase-12 protein in osteoblasts. Therefore, the osteoblastic cell line MC3T3-E1 was challenged to investigate any impact of caspase-12 on the osteogenic pathways. Pharmacological inhibition of caspase-12 in MC3T3-E1 cells caused a statistically significant decrease in expression of some major osteogenic genes, including those for alkaline phosphatase, osteocalcin and Phex. This downregulation was further confirmed by an alkaline phosphatase activity assay and by a siRNA inhibition approach. Altogether, this study demonstrates caspase-12 expression and points to its unknown physiological engagement in bone cells during the course of craniofacial development.
Highlights
Caspases are evolutionary conserved proteases traditionally associated with apoptosis and inflammation (Van Opdenbosch and Lamkanfi, 2019)
Since caspase-12 was strongly present in osteoblasts and since a strong impact on osteoblastic differentiation was demonstrated after general inhibition of the caspases (Mogi and Togari, 2003; Kratochvílová et al, 2020), our aim was to determine whether caspase-12 participates in modulation of the osteogenic pathways
To ascertain the increase in Casp12 mRNA expression between stages E13 and E15, at the protein level and precise caspase-12 localization, immunofluorescent analyses were performed on the developing mandibular bone at the area surrounding the first molar
Summary
Caspases are evolutionary conserved proteases traditionally associated with apoptosis and inflammation (Van Opdenbosch and Lamkanfi, 2019). Particular attention has been paid to their novel roles in other processes, such as differentiation, proliferation or autophagy (Shalini et al, 2015; Nakajima and Kuranaga, 2017; Tsapras and Nezis, 2017). The most common investigated caspases include apical proapoptotic caspase-8 and caspase-9, pro-inflammatory caspase-1, and the executive caspases-3 and -7, while others are rather neglected. Caspase-12 is usually ranked as an inflammatory caspase (Bolívar et al, 2019), its exact effect remains unknown. Studies have suggested the participation of caspase-12 in endoplasmic reticulum stress-induced apoptosis (Nakagawa et al, 2000; Shiraishi et al, 2006)
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