Synergistic Interactions between Grafted Hyaluronic Acid and Lubricin Provide Enhanced Wear Protection and Lubrication

Das, Saurabh; Banquy, Xavier; Zappone, Bruno; Greene, George W.; Jay, Gregory D.; Israelachvili, Jacob N.

doi:10.1021/bm400327a

Cited by 146 publications

(200 citation statements)

References 41 publications

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“…This idea is in agreement with previous studies reporting that both wear protection and friction forces are highly sensitive to LUB concentration. 18,26,43 Although they exhibited the highest friction coefficients among all tribosystems studied, FN+ESF films provided effective wear protection of surfaces (similar to that observed for FN+LUB films). This finding reaffirms that coefficients of friction and wear protection are not necessarily related to each other.…”

Section: ■ Discussionsupporting

confidence: 57%

Fibronectin mediates enhanced wear protection of lubricin during shear

et al. 2015

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Fibronectin (FN) is a glycoprotein found in the superficial zone of cartilage; however, its role in the lubrication and the wear protection of articular joints is unknown. In this work, we have investigated the molecular interactions between FN and various components of the synovial fluid such as lubricin (LUB), hyaluronan (HA), and serum albumin (SA), which are all believed to contribute to joint lubrication. Using a Surface Forces Apparatus, we have measured the normal (adhesion/repulsion) and lateral (friction) forces across layers of individual synovial fluid components physisorbed onto FN-coated mica substrates. Our chief findings are (i) FN strongly tethers LUB and HA to mica, as indicated by high and reversible long-range repulsive normal interactions between surfaces, and (ii) FN and LUB synergistically enhance wear protection of surfaces during shear, as suggested by the structural robustness of FN+LUB layers under pressures up to about 4 MPa. These findings provide new insights into the role of FN in the lubricating properties of synovial fluid components sheared between ideal substrates and represent a significant step forward in our understanding of cartilage damage involved in diseases such as osteoarthritis.

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Section: ■ Discussionsupporting

confidence: 57%

Fibronectin mediates enhanced wear protection of lubricin during shear

et al. 2015

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“…Our studies clearly identify EGFR signaling as an important pathway that promotes the production of Prg4 at the cartilage surface. Many studies suggest a synergistic interaction between Prg4 and HA to promote more effective boundary lubrication (21)(22)(23). Interestingly, our data reveal that both lubricants are remarkably decreased in EGFR-deficient joints.…”

Section: Discussionmentioning

confidence: 50%

EGFR signaling is critical for maintaining the superficial layer of articular cartilage and preventing osteoarthritis initiation

Jia

Tong

et al. 2016

Proc. Natl. Acad. Sci. U.S.A.

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Osteoarthritis (OA) is the most common joint disease, characterized by progressive destruction of the articular cartilage. The surface of joint cartilage is the first defensive and affected site of OA, but our knowledge of genesis and homeostasis of this superficial zone is scarce. EGFR signaling is important for tissue homeostasis. Immunostaining revealed that its activity is mostly dominant in the superficial layer of healthy cartilage but greatly diminished when OA initiates. To evaluate the role of EGFR signaling in the articular cartilage, we studied a cartilage-specific Egfr-deficient (CKO) mouse model (Col2-Cre EgfrWa5/flox). These mice developed early cartilage degeneration at 6 mo of age. By 2 mo of age, although their gross cartilage morphology appears normal, CKO mice had a drastically reduced number of superficial chondrocytes and decreased lubricant secretion at the surface. Using superficial chondrocyte and cartilage explant cultures, we demonstrated that EGFR signaling is critical for maintaining the number and properties of superficial chondrocytes, promoting chondrogenic proteoglycan 4 (Prg4) expression, and stimulating the lubrication function of the cartilage surface. In addition, EGFR deficiency greatly disorganized collagen fibrils in articular cartilage and strikingly reduced cartilage surface modulus. After surgical induction of OA at 3 mo of age, CKO mice quickly developed the most severe OA phenotype, including a complete loss of cartilage, extremely high surface modulus, subchondral bone plate thickening, and elevated joint pain. Taken together, our studies establish EGFR signaling as an important regulator of the superficial layer during articular cartilage development and OA initiation.EGFR | articular cartilage | chondrocyte | lubrication | osteoarthritis

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“…to compensate for lubricin loss. Recent studies have indicated that hyaluronan acts synergistically with lubricin to provide friction reduction and greater wear protection in certain experimental conditions (Das et al, 2013). Our study would suggest that increased Has2 expression is not sufficient to prevent the articular cartilage damage and dysfunction seen in Prg4 mutant mice.…”

Section: Discussionmentioning

confidence: 64%

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

Koyama¹,

Saunders²,

Salhab

et al. 2014

J Dent Res

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The Proteoglycan 4 (Prg4) product lubricin plays essential roles in boundary lubrication and movement in limb synovial joints, but its roles in temporomandibular joint (TMJ) are unclear. Thus, we characterized the TMJ phenotype in wild-type and Prg4 -/-mouse littermates over age. As early as 2 weeks of age, mutant mice exhibited hyperplasia in the glenoid fossa articular cartilage, articular disc, and synovial membrane. By 1 month of age, there were fewer condylar superficial tenascin-C/ Col1-positive cells and more numerous apoptotic condylar apical cells, while chondroprogenitors displayed higher mitotic activity, and Sox9-, Col2-, and ColX-expressing chondrocyte zones were significantly expanded. Mutant subchondral bone contained numerous Catepsin K-expressing osteoclasts at the chondro-osseous junction, increased invasive marrow cavities, and suboptimal subchondral bone. Mutant glenoid fossa, disc, synovial cells, and condyles displayed higher Hyaluronan synthase 2 expression. Mutant discs also lost their characteristic concave shape, exhibited ectopic chondrocyte differentiation, and occasionally adhered to condylar surfaces. A fibrinoid substance of unclear origin often covered the condylar surface. By 6 months of age, mutant condyles displayed osteoarthritic degradation with apical/mid-zone separation. In sum, lubricin exerts multiple essential direct and indirect roles to preserve TMJ structural and cellular integrity over post-natal life.

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Synergistic Interactions between Grafted Hyaluronic Acid and Lubricin Provide Enhanced Wear Protection and Lubrication

Cited by 146 publications

References 41 publications

Fibronectin mediates enhanced wear protection of lubricin during shear

Fibronectin mediates enhanced wear protection of lubricin during shear

EGFR signaling is critical for maintaining the superficial layer of articular cartilage and preventing osteoarthritis initiation

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

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