The role of CCN2 in cartilage and bone development

CCN2, a classical member of the CCN family of matricellular proteins, is a key molecule that conducts cartilage development in a harmonized manner through novel molecular actions. During vertebrate development, all cartilage is primarily formed by a process of mesenchymal condensation, while CCN2 is induced to promote this process. Afterwards, cartilage develops into several subtypes with different fates and missions, in which CCN2 plays its proper roles according to the corresponding microenvironments. The history of CCN2 in cartilage and bone began with its re-discovery in the growth cartilage in long bones, which determines the skeletal size through the process of endochondral ossification. CCN2 promotes physiological developmental processes not only in the growth cartilage but also in the other types of cartilages, i.e., Meckel’s cartilage representing temporary cartilage without autocalcification, articular cartilage representing hyaline cartilage with physical stiffness, and auricular cartilage representing elastic cartilage. Together with its significant role in intramembranous ossification, CCN2 is regarded as a conductor of skeletogenesis. During cartilage development, the CCN2 gene is dynamically regulated to yield stage-specific production of CCN2 proteins at both transcriptional and post-transcriptional levels. New functional aspects of known biomolecules have been uncovered during the course of investigating these regulatory systems in chondrocytes. Since CCN2 promotes integrated regeneration as well as generation (=development) of these tissues, its utility in regenerative therapy targeting chondrocytes and osteoblasts is indicated, as has already been supported by experimental evidence obtained in vivo

miR-17–92 cluster: ups and downs in cancer and aging

The miR-17–92 cluster encoding 6 single mature miRNAs was identified a couple of years ago to contain the first oncogenic miRNAs. Now, one of these 6 miRNAs, miR-19 has been identified as the key responsible for this oncogenic activity. This in turn reduces PTEN levels and in consequence activates the AKT/mTOR pathway that is also prominently involved in modulation of organismal life spans. In contrast, miR-19 and other members of the miR-17–92 cluster are found to be commonly downregulated in several human replicative and organismal aging models. Taken together, these findings suggest that miR-19 and the other members of the miR-17–92 cluster might be important regulators on the cross-roads between aging and cancer. Therefore, we here briefly summarize how this cluster is transcriptionally regulated, which target mRNAs have been confirmed so far and how this might be linked to modulation of organismal life-spans

Tumor necrosis factor-alpha as a possible auto-/paracrine factor affecting estrous cycle in the cat uterus

Tumor Necrosis Factor-alpha (TNFα) is a pleiotrophic cytokine, affects either normal or tumor cells, and influences cellular differentiation. TNFα role in female reproduction has been proven to be mediated through an influence on prostaglandin (PGs) synthesis and output. To evaluate the possible role of TNFα in an auto-/paracrine regulation in the cat uterus, mRNA expression coding for TNFα and its receptors (TNFR1 and TNFR2), and TNFα protein content at different stages of the estrous cycle were investigated. Additionally, TNFα involvement in PG secretion at different stages of the estrous cycle was investigated by in vitro tissue culture. Gene expressions coding for TNFα and TNFR1 were the highest at diestrus (P < 0.05). TNFα protein expression was the lowest at interestrus (P < 0.05). Nevertheless, TNFR2 was not affected by the estrous stage. TNFα at a dose of 1 ng/ml significantly increased PGF₂α secretion at estrus (P < 0.01) and PGE₂ secretion at diestrus (P < 0.001) after 12h incubation. Overall findings indicate that TNFα locally produced in the cat’s uterus, stimulates PG secretion in an estrous cycle-related manner