Role of lubricin and boundary lubrication in the prevention of chondrocyte apoptosis

Abstract

Osteoarthritis is a complex disease involving the mechanical breakdown of articular cartilage in the presence of altered joint mechanics and chondrocyte death, but the connection between these factors is not well established. Lubricin, a mucinous glycoprotein encoded by the PRG4 gene, provides boundary lubrication in articular joints. Joint friction is elevated and accompanied by accelerated cartilage damage in humans and mice that have genetic deficiency of lubricin. Here, we investigated the relationship between coefficient of friction and chondrocyte death using ex vivo and in vitro measurements of friction and apoptosis. We observed increases in whole-joint friction and cellular apoptosis in lubricin knockout mice compared with wild-type mice. When we used an in vitro bovine explant cartilage-on-cartilage bearing system, we observed a direct correlation between coefficient of friction and chondrocyte apoptosis in the superficial layers of cartilage. In the bovine explant system, the addition of lubricin as a test lubricant significantly lowered the static coefficient of friction and number of apoptotic chondrocytes. These results demonstrate a direct connection between lubricin, boundary lubrication, and cell survival and suggest that supplementation of synovial fluid with lubricin may be an effective treatment to prevent cartilage deterioration in patients with genetic or acquired deficiency of lubricin.camptodactyly-arthropathy-coxa vara-pericarditis | shear strain | antiadhesion | tribology

Induced superficial chondrocyte death reduces catabolic cartilage damage in murine posttraumatic osteoarthritis

“…These data indicate that cartilage damage, attributable to altered biomechanics in the DMM model, is a proximate cause of chondrocyte loss. Other studies have suggested that material damage to the cartilage surface is another antecedent of chondrocyte death (28)(29)(30). For example, depletion of surface lubrication in human cartilage explants caused exaggerated mechanical strain (29) and depletion in bovine cartilage explants resulted in increased chondrocyte apoptosis following mechanical loading and movement (28).…”

“…Other studies have suggested that material damage to the cartilage surface is another antecedent of chondrocyte death (28)(29)(30). For example, depletion of surface lubrication in human cartilage explants caused exaggerated mechanical strain (29) and depletion in bovine cartilage explants resulted in increased chondrocyte apoptosis following mechanical loading and movement (28). Genetic deficiency of Prg4, which increases cartilage surface friction and causes wear (30), also leads to a progressive loss of chondrocytes (31).…”

Lubricin is Required for the Structural Integrity and Post-natal Maintenance of TMJ

“…Prg4 null mice recapitulate the CACP joint phenotype and display synovial joint deterioration, synovial membrane hyperplasia, articular cartilage fibrillations, abnormal protein deposition, and disappearance of superficial zone cells (Rhee et al, 2005;Novince et al, 2012a,b). Thus, in addition to boundary lubrication, lubricin may prevent cell/ protein adhesion, regulate proliferation of synovial cells and protect superficial chondrocytes from death (Rhee et al, 2005;Waller et al, 2013). Recent studies showed that exogenously introduced recombinant lubricin or Prg4 overexpression provides chondroprotection and lubrication in mouse models of osteoarthritis (OA), suggesting that exogenous lubricin could be a joint therapeutic (Flannery et al, 2009;Ruan et al, 2013).…”

Enhancing adipose stem cell chondrogenesis: A study on the roles of dexamethasone, transforming growth factor β3 and ascorbate supplements and their combination

“…Lubricin, a surface-active mucinous glycoprotein, provides articular joint lubrication [70] and prevents chondrocyte apoptosis [71]. Based on our indings, we suggest the use of Dex as a factor to increase lubricin mRNA expression.…”