Tuesday, September 28, 2010


PTN is upregulated by LSJL.

Effects of pleiotrophin, a heparin-binding growth factor, on human primary and immortalized chondrocytes.

"Pleiotrophin (PTN) is a secreted heparin-binding peptide expressed in mesodermal and neuroectodermal cells during development, but rarely in adult tissues. In fetal and juvenile, but not in mature cartilage, PTN is abundant. PTN is re-expressed in chondrocytes in early stages of osteoarthritis (OA). we investigated the occurrence of PTN receptors in human articular cartilage in situ and PTN effects on human primary and immortalized chondrocytes in vitro.
Of the putative PTN signaling receptors, immortalized and primary chondrocytes (pc) expressed the anaplastic lymphoma kinase (ALK), less the receptor-type protein tyrosine phosphatase zeta/beta (PTPzeta). ALK expression was upregulated upon ligand exposure. PTN stimulation activated the AP-1 (activator protein-1) transcription factor and altered gene expression{so AP-1 transcription factor was likely upregulated in LSJL}. Prolonged stimulation induced PTN mRNA expression slightly, reduced vascular endothelial growth factor (VEGF) mRNA as well as NO production. Whereas mRNA expression of matrix metalloproteinases (MMPs) MMP-1 and MMP-13 was reduced, their inhibitors TIMP-1{upregulated by LSJL} and TIMP-2 were induced. PTN stimulated chondrocyte migration and proliferation.
PTN is an autocrine growth factor in cartilage. PTN may be involved in the clustering and proliferation of chondrocytes observed in the early stages of OA."

"Together with midkine (MK) [PTN] forms a family of heparin-binding proteins that are normally expressed during embryogenesis, but only at low levels in healthy adult tissues."

"Both, PTN and MK bind with high-affinity to extracellular heparan-sulfate proteoglycans as well as to cell surface syndecans, LDL receptor-related protein (LRP), anaplastic lymphoma kinase (ALK), and the receptor-type protein tyrosine phosphatase ζ/β (PTPζ)"

"PTN increased 3H-thymidine incorporation to about 150% of controls in C28/I2"

According to Pleiotrophin regulates the retention and self-renewal of hematopoietic stem cells in the bone marrow vascular niche., PTN is involved in the homing and retention of HSCs.  So the upregulation of HSCs could indicate the presence of more HSCs in LSJL.

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