Bioregulation of lubricin expression by growth factors and cytokines

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.