CCN2 (Cellular Communication Network factor 2) in the bone marrow microenvironment,normal and malignant hematopoiesis

CCN2, formerly termed Connective Tissue Growth Factor, is a protein belonging to the Cellular Communication Network (CCN)-family of secreted extracellular matrix-associated proteins. As a matricellular protein it is mainly considered to be active as a modifier of signaling activity of several different signaling pathways and as an orchestrator of their cross-talk. Furthermore, CCN2 and its fragments have been implicated in the regulation of a multitude of biological processes, including cell proliferation, differentiation, adhesion, migration, cell survival, apoptosis and the production of extracellular matrix products, as well as in more complex processes such as embryonic development, angiogenesis, chondrogenesis, osteogenesis, fibrosis, mechanotransduction and inflammation. Its function is complex and context dependent, depending on cell type, state of differentiation and microenvironmental context. CCN2 plays a role in many diseases, especially those associated with fibrosis, but has also been implicated in many different forms of cancer. In the bone marrow (BM), CCN2 is highly expressed in mesenchymal stem/stromal cells (MSCs). CCN2 is important for MSC function, supporting its proliferation, migration and differentiation. In addition, stromal CCN2 supports the maintenance and longtime survival of hematopoietic stem cells, and in the presence of interleukin 7, stimulates the differentiation of pro-B lymphocytes into pre-B lymphocytes. Overexpression of CCN2 is seen in the majority of B-acute lymphoblastic leukemias, especially in certain cytogenetic subgroups associated with poor outcome. In acute myeloid leukemia, CCN2 expression is increased in MSCs, which has been associated with leukemic engraftment in vivo. In this review, the complex function of CCN2 in the BM microenvironment and in normal as well as malignant hematopoiesis is discussed. In addition, an overview is given of data on the remaining CCN family members regarding normal and malignant hematopoiesis, having many similarities and some differences in their function.     

Pro‐inflammation and pro‐fibrosis factors were highly induction in heart tissues of carotid arteries balloon‐injured animal model

To investigate the changes of cardiomyocyte inflammation and fibrosis factors in heart of carotid artery balloon injury inflammatory rat model. Using rat carotid artery balloon injury model to detect left ventricular characteristics at 2 h, 2 days and 14 days after surgery using hematoxylin‐eosin (H&E) gross stain, Masson's trichome stain and Western blot analysis for inflammatory and fibrosis‐induced factors, tumour necrosis factor α (TNFα), JNK1, P38α, connective tissue growth factor (CTGF), SP1 and transforming growth factor β (TGFβ) protein expressions. The rat carotid arteries were injured after 2 h, 2 days and 14 days. Balloon‐angioplasty to H&E stain results showed the increasing trend of left ventricular wall at 2 h and 2 days; then, the left ventricular wall became thinner, and the left ventricular chamber became enlarged and dilated after 14 days of carotid artery balloon injury. In addition, the Masson's trichome stain results showed that the left ventricular section has fibrosis‐related blue staining (collagen) at 2 and 14 days after rat carotid artery balloon injury, and became even more severe at 14 days. Furthermore, we observed the protein expression level changs, which include TNFα, JNK1, P38α, CTGF, SP1 and TGFβ using Western blotting assay. All proteins were induced at 2 h, 2 days and then reached the maximal level at 14 days. The vessel inflammation was associated with cardiac inflammatory and fibrosis effects during or after carotid artery balloon injury. Copyright © 2012 John Wiley & Sons, Ltd.     

CTGF facilitates cell‐cell communication in chondrocytes via PI3K/Akt signalling pathway

PurposesGap junction intercellular communication (GJIC) is essential for articular cartilage to respond appropriately to physical or biological stimuli and maintain homeostasis. Connective tissue growth factor (CTGF), identified as an endochondral ossification genetic factor, plays a vital role in cell proliferation, migration and adhesion. However, how CTGF regulates GJIC in chondrocytes is still unknown. This study aims to explore the effects of CTGF on GJIC in chondrocytes and its potential biomechanism.Materials and methodsqPCR was performed to determine the expression of gene profile in the CCN family in chondrocytes. After CTGF treatment, CCK‐8 assay and scratch assay were performed to explore cell proliferation and migration. A scrape loading/dye transfer assay was adopted to visualize GJIC in living chondrocytes. Western blot analysis was done to detect the expression of Cx43 and PI3K/Akt signalling. Immunofluorescence staining was used to show protein distribution. siRNA targeting CTGF was used to detect the influence on cell‐cell communication.ResultsThe CTGF (CCN2) was shown to be the highest expressed member of the CCN family in chondrocytes. CTGF facilitated functional gap junction intercellular communication in chondrocytes through up‐regulation of Cx43 expressions. CTGF activated PI3K/Akt signalling to promote Akt phosphorylation and translocation. Suppressing CTGF also reduced the expression of Cx43. The inhibition of PI3K/Akt signalling decreased the expressions of Cx43 and thus impaired gap junction intercellular communication enhanced by CTGF.ConclusionsFor the first time, we provide evidence to show CTGF facilitates cell communication in chondrocytes via PI3K/Akt signalling pathway.