Saturday, September 4, 2010


Cytokine-like 1 (Cytl1) regulates the chondrogenesis of mesenchymal cells.

"Cytokine-like 1 (Cytl1) [is] in bone marrow-derived CD34-positive cells. Cytl1 is predominantly expressed in chondrocytes and cartilage. Cytl1 expression was very low in mesenchymal cells, dramatically increased during chondrogenesis, and decreased during hypertrophic maturation, both in vivo and in vitro. The role of Cytl1 in chondrogenesis and hypertrophic maturation was examined by treating chondrifying mesenchymal cells with exogenous Cytl1 or ectopic expression of Cytl1. Exogenous Cytl1 caused chondrogenic differentiation of mouse limb bud mesenchymal cells during micromass culture. Lentivirus-mediated overexpression of Cytl1 additionally induced chondrogenic differentiation of mesenchymal cells. Cytl1 did not affect the hypertrophic maturation of chondrocytes. Cytl1 exerted its chondrogenic effect via stimulation of Sox9 transcriptional activity. Cytl1 caused expression of insulin-like growth factor 1, which has a capacity to induce chondrogenesis."

Cytl1 was expressed in days 3-6 of chondrogenesis heavily.  No Cytl1 upregulation was detection with LSJL. 

"Sox9 transcriptional activity is controlled by protein-protein interactions, for instance, positive modulation by factors such as cAMP-response element-binding protein-binding protein (CREB/p300) and peroxisome proliferator-activated receptor γ co-activator 1α (PGC-1α)"

Identification of CCR2-binding features in Cytl1 by a CCL2-like chemokine model.

"Chemokines are small secreted proteins that play an important role in immune responses and [are] involved in cartilage development. They present a conserved 3D structure, so-called IL8-like chemokine fold, which is supported by conserved cysteines forming intra-molecular disulfide bonds. Cytl1 might adopt a 4-helical cytokine fold. Cytl1 is more likely to adopt an IL8-like chemokine fold, in particular similar to CCL2 {LSJL upregulates CCL2 3.691 fold} (monocyte chemoattractant protein 1, MCP-1). Moreover, we identify in a CCL2-like 3D model of Cytl1 the necessary reported features to signal through the chemokine receptor CCR2. Cytl1 could be a structurally and functionally related analog of CCL2 signaling through the chemokine receptor CCR2."

So LSJL could induce chondrogenesis through CCL2 rather than Cytl1.

Cytl1 is also mentioned to having similarities to GM-CSF.

"we generated a Cytl1 knock-out (Cytl1(-/-)) mouse to investigate the in vivo role of Cytl1. Deletion of the Cytl1 gene did not affect chondrogenesis or cartilage development. Cytl1(-/-) mice also showed normal endochondral ossification and long bone development. Ultrastructural features of articular cartilage, such as matrix organization and chondrocyte morphology, were similar in wild-type and Cytl1(-/-) mice.  Cytl1(-/-) mice were more sensitive to osteoarthritic (OA) cartilage destruction. Compared with wild-type littermates, Cytl1(-/-) mice showed more severe OA cartilage destruction upon destabilization of the medial meniscus of mouse knee joints. Expression levels of Cytl1 were markedly decreased in OA cartilage of humans and experimental mice. Rather than regulating cartilage and bone development, Cytl1 is required for the maintenance of cartilage homeostasis, and loss of Cytl1 function is associated with experimental OA cartilage destruction in mice."

"Expression patterns of the chondrocyte markers Col2a1, aggrecan (Acan), chondromodulin 1 (Lect1), Sox9, and Igf1, and Sox9 transcriptional activity were similar between WT and Cytl1−/− cell"

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