2007 Volume No 13 pages 40-45
Title: Bioregulation of lubricin expression by growth
factors and cytokines |
Author: ARC Jones, CR Flannery |
Address: Department of Women's Health & Musculoskeletal
Biology, Wyeth Research, Cambridge, MA 02140, USA |
E-mail: cflannery at wyeth.com |
Key Words: articular cartilage, chondrocyte, cytokine,
growth factor, lubricin, osteoarthritis, proteoglycan 4 (PRG4),
superficial zone protein (SZP), synovial joint, synoviocyte |
Publication date: March 20th 2007 |
Abstract: Lubricin, also commonly referred to as
superficial zone protein (SZP) and proteoglycan 4 (PRG4),
is a multifaceted, cytoprotective glycoprotein that contributes
to the boundary lubrication properties facilitating low friction
levels at interfacing surfaces of articular cartilage. Biological
processes effecting the gain or loss of lubricin function
may therefore have important consequences relevant to joint
physiology and pathology. Herein, we describe experiments
conducted to extend our understanding of the influence of
various cytokines and growth factors on lubricin gene expression
and protein secretion in synovial tissues. Exposure of synoviocytes,
chondrocytes and cartilage explants to proinflammatory cytokines
such as interleukin-1 (IL-1) and tumor necrosis factor-alpha
(TNF-alpha) results in a marked reduction in the expression
and/or abundance of secreted lubricin, with corresponding
alterations in the amounts of cartilage-associated (boundary)
lubricin. Conversely, treatment with transforming growth factor-beta
(TGF-beta) significantly upregulates lubricin synthesis, secretion
and cartilage boundary association. Oncostatin M also appears
to be capable of modulating lubricin metabolism, with the
potential to induce lubricin synthesis by chondrocytes. Collectively,
the results of studies on cytokine and growth factor regulation
of lubricin biosynthesis and biodistribution may help provide
new insights and therapeutic perspectives for promoting joint
function. |
Article download: Pages
40-45 (PDF file) |