Modulation of lubricin biosynthesis and tissue surface properties following cartilage mechanical injury

Abstract

Objective. To evaluate the effects of injurious compression on the biosynthesis of lubricin at different depths within articular cartilage and to examine alterations in structure and function of the articular surface following mechanical injury.Methods. Bovine cartilage explants were subdivided into level 1, with intact articular surface, and level 2, containing middle and deep zone cartilage. Following mechanical injury, lubricin messenger RNA (mRNA) levels were monitored by quantitative reverse transcriptase-polymerase chain reaction, and soluble or cartilage-associated lubricin protein was analyzed by Western blotting and immunohistochemistry. Cartilage morphology was assessed by histologic staining, and tissue functionality was assessed by friction testing.Results. Two days after injury, lubricin mRNA expression was up-regulated ϳ3-fold for level 1 explants and was down-regulated for level 2 explants. Lubricin expression in level 1 cartilage returned to control levels after 6 days in culture. Similarly, lubricin protein synthesis and secretion increased in response to injury for level 1 explants and decreased for level 2 cartilage. Histologic staining revealed changes in the articular surface of level 1 explants following injury, with respect to glycosaminoglycan and collagen content. Injured level 1 explants displayed an increased coefficient of friction relative to controls. Conclusion. Our findings indicate that increased lubricin biosynthesis appears to be an early transient response of surface-layer cartilage to injurious compression. However, distinct morphologic changes occur with injury that appear to compromise the frictional properties of the tissue.Osteoarthritis (OA) is characterized by the degeneration of articular cartilage, leading to matrix fibrillation, fissuring, and the development of lesions. In the final stages of the disease, erosion of cartilage leads to painful bone-on-bone contact. The etiology of OA is complex and involves multiple biochemical, biomechanical, and genetic factors in addition to aging (1-3). Cartilage injury in young individuals is a prominent predisposing factor leading to increased risk of the subsequent development of OA (4,5) and, as such, represents a discrete pathologic event. Damage to the meniscus or ligaments sustained during traumatic joint injury causes instability, subjecting articular cartilage to abnormal biomechanical forces and resulting in the release of mediators of inflammation (6). Several animal models of OA are thus based on the observation that joint instability, i.e., via anterior cruciate ligament transaction or perturbation of the meniscus (7), results in the rapid onset of articular cartilage degeneration with an OA-like phenotype. The initial events following joint injury are thought to be crucial, since surgical interventions to restore joint stability do not seem to reduce the risk of developing posttraumatic OA (8).

Alteration of articular cartilage frictional properties by transforming growth factor β, interleukin‐1β, and oncostatin M

“…Boundary lubrication was clearly regulated by treatments known to promote accumulation of lubricants on the tissue surface. Boundary mode lubrication is most likely to occur at slow speeds, often at the beginning of the gait cycle after the joint has experienced high loads for sustained periods of time (24,51). In boundary mode, eq is highest, and as such, tissue damage is most likely to occur.…”

Mechanical motion promotes expression of Prg4 in articular cartilage via multiple CREB-dependent, fluid flow shear stress-induced signaling pathways

“…Because Prg4 GFPCreERt2/+ ; Rosa26 floxlacZ/+ mice were housed in either the absence or presence of a running wheel for 1 mo, after which their knees were isolated, fixed, sectioned, and immunostained to assay cellular localization of either phospho-S133 CREB (D) or CRTC1 (E). expression in the articular cartilage both has been noted to be sensitive to mechanical loading (Nugent et al 2006a,b;Jones et al 2009) and was recently found to protect against the development of osteoarthritis (Ruan et al 2013), we wondered whether voluntary wheel running might induce the expression of Prg4 in articular cartilage and thereby slow the progression of osteoarthritis. By employing Prg4…”

“…While Wnt/b-catenin signaling has been found to be essential for expression of Prg4/lubricin during early development (Koyama et al 2008;Yasuhara et al 2011), the signals that maintain the expression of this locus in adult articular cartilage remain obscure. Studies have pointed to a role for both TGF-b signaling (Lee et al 2008) and mechanical loading (Nugent et al 2006a,b;Jones et al 2009) in the maintenance of Prg4/ lubricin expression in either newborn or adult articular cartilage. In this study, we both document that voluntary wheel running induces the expression of the Prg4 locus in the superficial zone of knee joint articular cartilage and identify multiple signaling pathways downstream from fluid flow shear stress (FFSS) that promote the expression of Prg4 in this tissue in a CREB-dependent manner.…”

Mechanical injury potentiates proteoglycan catabolism induced by interleukin‐6 with soluble interleukin‐6 receptor and tumor necrosis factor α in immature bovine and adult human articular cartilage

“…However, other aspects of chondrocyte response to injury may be very different in the superficial zone versus deeper layers, such as the marked up-regulation of lubricin reported in the superficial zone but not in the middle zone of similar bovine tissue (49). Additionally, the local strains in the most superficial region of human cartilage samples could be much higher than those in the bovine samples from the middle zone because of the highly compliant region just below the intact surface zone (50).…”