The slippery slope of arthritis

Abstract

Farshid GuilakThe synovial joint is one of nature’s true marvels,boasting frictional properties that remain unmatched byhuman-made joints. The coefficient of friction ( for its lubricating properties, and early studies showed)ofcartilage gliding on cartilage has been measured to be aslow as 0.002 (1,2), meaning that a contact force of1,000N ( 225 pounds) across the joint produces africtional shear force that is 1/500th of this value, or just2N ( 0.45 pounds) at the cartilage surface (see Table 1 forexamples of values for other common joint materials).Such low frictional properties provide for a load-bearingsurface that, under normal circumstances, exhibits virtuallyno wear over tens of millions of cycles of use, whilewithstanding loads of several times the body weight.The mechanisms by which the synovial jointachieves these frictional properties involve an intricatecombination of biomechanical and biomolecular factorsacting at a variety of scales. For example, congruity ofthe joint surfaces serves to distribute joint loading over alarger contact area, thereby minimizing contact stresses.Furthermore, the high water content and low permeabil-ity of the cartilage extracellular matrix provide a uniquemechanism of supporting loads (3), whereby fluid pres-surization within the tissue can bear nearly 90% of theload, greatly minimizing the stresses on the solid extra-cellular matrix (4,5). Synovial fluid plays multiple rolesinjointlubricationbyprovidingahighviscosity“squeezefilm” layer that delays cartilage-to-cartilage contact un-der dynamic loading (6,7) as well as a source of bound-ary lubricant molecules for the cartilage surface. Bound-ary lubricants are molecules that are adsorbed or bound tothe joint surface, potentially as a single layer. This layer ofmolecules on each side of the joint transmits loads to thetissue and provides a mechanism for decreasing frictiononce the tissue surfaces actually come in contact with oneanother. Indeed, the lubricating properties of synovial fluidled investigators to hypothesize even decades ago thatspecific moieties present in synovial fluid were responsibleevidence of the loss of these lubricating properties withosteoarthritis or rheumatoid arthritis (8).In the last 2 decades, a wealth of information hasemerged on the composition, structure, and propertiesof molecules present in the synovial fluid and thecartilage surface that serve as the primary boundarylubricants of the synovial joint. The first such molecule,an 227-kd glycoprotein termed lubricin (9), was iden-tified from bovine synovial fluid by density-gradientsedimentation and gel-permeation chromatography.Surprisingly, purified lubricin was found to lubricatearticular cartilage as effectively as whole synovial fluid.This molecule is a product of synovial fibroblasts ex-pressing the megakaryocyte-stimulating factor (MSF)gene(alsotermed