Loss of cartilage structure, stiffness, and frictional properties in mice lacking PRG4

Abstract

ObjectiveTo assess the role of the glycoprotein PRG4 in joint lubrication and chondroprotection by measuring friction, stiffness, surface topography, and subsurface histology of the hip joints of Prg4−/− and wild-type (WT) mice.MethodsFriction and elastic modulus were measured in cartilage from the femoral heads of Prg4−/− and WT mice ages 2, 4, 10, and 16 weeks using atomic force microscopy, and the surface microstructure was imaged. Histologic sections of each femoral head were stained and graded.ResultsHistologic analysis of the joints of Prg4−/− mice showed an enlarged, fragmented surface layer of variable thickness with Safranin O–positive formations sometimes present, a roughened underlying articular cartilage surface, and a progressive loss of pericellular proteoglycans. Friction was significantly higher on cartilage of Prg4−/− mice at age 16 weeks, but statistically significant differences in friction were not detected at younger ages. The elastic modulus of the cartilage was similar between cartilage surfaces of Prg4−/− and WT mice at young ages, but cartilage of WT mice showed increasing stiffness with age, with significantly higher moduli than cartilage of Prg4−/− mice at older ages.ConclusionDeletion of the gene Prg4 results in significant structural and biomechanical changes in the articular cartilage with age, some of which are consistent with osteoarthritic degeneration. These findings suggest that PRG4 plays a significant role in preserving normal joint structure and function.

Human Synovial Lubricin Expresses Sialyl Lewis x Determinant and Has L-selectin Ligand Activity

“…It has been reported that low expression levels of lubricin were associated with a strong synovial stromal activation (22), characterized by the infiltration of T cells and macrophages, and was associated with a higher destructive potential and a worse prognosis (63). Prg4 knock-out mice exhibited a degenerative phenotype, including synovial hyperplasia and abnormal cartilage surface (64).…”

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

“…Boundary lubrication dominates during periods of high load and low velocity, when the lubricant film layer is thinner than the surface roughness (16). In healthy articular joints, a layer of lubricin molecules covers the surface of cartilage and acts as an antiadhesive and boundary lubricant to prevent cartilage damage as surface asperities move against each other (17)(18)(19)(20). Patients with the autosomal recessive disease camptodactyly-arthropathy-coxa vara-pericarditis syndrome (CACP) lack functional lubricin and develop precocious cartilage failure.…”

CACP syndrome: identification of five novel mutations and of the first case of UPD in the largest European cohort

“…8 In addition, the deletion of the gene Prg4 in mice resulted in significant structural and biomechanical changes in the articular cartilage with age, some of which are consistent with osteoarthritic degeneration. 9 Lubricin contains multiple domains, in particular the large central mucin-like domain encoded by exon 6, which is rich of repeated motifs for post-translationally O-linked glycosylation. 10 This region is thought to be the lubricating domain of lubricin, as the sequential removal of the last sugars results in loss of boundary lubricating ability.…”