Lubricin as a novel nanostructured protein coating to reduce fibroblast density

Aninwene, George E.; Yang, Zifan; Ravi, V. Nathan; Jay, Gregory D.; Webster, Thomas J.

doi:10.2147/ijn.s56439

Cited by 6 publications

(1 citation statement)

References 14 publications

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“…In addition to being an impressive biological lubricant, LUB exhibits a number of interesting properties including excellent antiadhesive properties , and electrokinetic properties . These properties and the recent development of recombinant methods that allow LUB to be produced in large quantities have led to the development of LUB technologies for the treatment of arthritis and related conditions, − eye lubrication, antiadhesive coatings, ,, and low-fouling microfluidic systems . Despite this interest and rapid increase in technologies that take advantage of LUB’s interfacial properties, detailed knowledge on the self-assembled LUB layer structure is surprisingly sparse and has yet to be directly probed or visualized with most information inferred from indirect observations and circumstantial evidence.…”

Section: Introductionmentioning

confidence: 99%

Structure and Property Changes in Self-Assembled Lubricin Layers Induced by Calcium Ion Interactions

et al. 2017

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Lubricin (LUB) is a "mucin-like" glycoprotein found in synovial fluids and coating the cartilage surfaces of articular joints, which is now generally accepted as one of the body's primary boundary lubricants and antiadhesive agents. LUB's superior lubrication and antiadhesion are believed to derive from its unique interfacial properties by which LUB molecules adhere to surfaces (and biomolecules, such as hyaluronic acid and collagen) through discrete interactions localized to its two terminal end domains. These regionally specific interactions lead to self-assembly behavior and the formation of a well-ordered "telechelic" polymer brush structure on most substrates. Despite its importance to biological lubrication, detailed knowledge on the LUB's self-assembled brush structure is insufficient and derived mostly from indirect and circumstantial evidence. Neutron reflectometry (NR) was used to directly probe the self-assembled LUB layers, confirming the polymer brush architecture and resolving the degree of hydration and level of surface coverage. While attempting to improve the LUB contrast in the NR measurements, the LUB layers were exposed to a 20 mM solution of CaCl, which resulted in a significant change in the polymer brush structural parameters consisting of a partial denaturation of the surface-binding end-domain regions, partial dehydration of the internal mucin-domain "loop", and collapse of the outer mucin-domain surface region. A series of atomic force microscopy measurements investigating the LUB layer surface morphology, mechanical properties, and adhesion forces in phosphate-buffered saline and CaCl solutions reveal that the structural changes induced by calcium ion interactions also significantly alter key properties, which may have implications to LUB's efficacy as a boundary lubricant and wear protector in the presence of elevated calcium ion concentrations.

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Section: Introductionmentioning

confidence: 99%

Structure and Property Changes in Self-Assembled Lubricin Layers Induced by Calcium Ion Interactions

et al. 2017

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Two compartment pharmacokinetic model describes the intra‐articular delivery and retention of rhprg4 following ACL transection in the Yucatan mini pig

Hurtig

Zaghoul²,

Sheardown³

et al. 2018

Journal Orthopaedic Research

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Treatment of the injured joint with rhPRG4 is based on recent observations that inflammation diminishes expression of native PRG4. Re-establishing lubrication between pressurized and sliding cartilage surfaces during locomotion promotes the nascent expression of PRG4 and thus intra-articular (IA) treatment strategies should be supported by pharmacokinetic evidence establishing the residence time of rhPRG4. A total of 21 Yucatan minipigs weighing $55 kg each received 4 mg of 131 I-rhPRG4 delivered by IA injection 5 days following surgical ACL transection. Animals were sequentially euthanized following IA rhPRG4 at 10 min (time zero), 24, 72 h, 6, 13 and 20 days later. The decay of the 131 I-rhPRG4 was measured relative to a non-injected aliquot and normalized to the weight of cartilage samples, menisci and synovium, and known cartilage volumes from each compartment surface obtained from representative Yucatan minipig knees. Decay of 131 I-rhPRG4 from joint tissues best fit a two-compartment model with an a half-life (t 1/ 2a ) of 11.28 h and b half-life (t 1/2b ) of 4.81 days. The tibial and femoral cartilage, meniscii, and synovium retained 7.7% of dose at 24 h. High concentrations of rhPRG4 were found in synovial fluid (SF) that was non-aspiratable and resided on the articular surfaces, removable by irrigation, at 10 min following 131 I-rhPRG4 injection. Synovial fluid K21 exceeded K12 and SF t 1/2b was 28 days indicating SF is the reservoir for rhPRG4 following IA injection. Clinical Significance: rhPRG4 following IA delivery in a traumatized joint populates articular surfaces for a considerable period and may promote the native expression of PRG4. ß

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Interactions between Lubricin and Hyaluronic Acid Synergistically Enhance Antiadhesive Properties

Han

Huang

et al. 2019

ACS Appl. Mater. Interfaces

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Preventing the unwanted adsorption of proteins and cells at articular cartilage surfaces plays a critical role in maintaining healthy joints and avoiding degenerative diseases such as osteoarthritis. Immobilized at the surface of healthy articular cartilage is a thin, interfacial layer of macromolecules consisting mainly of hyaluronic acid (HA) and lubricin (LUB; a.k.a. PRG4) that is believed to form a co-adsorbed, composite film now known to exhibit synergistic tribological properties. Bioinspired by the composition of cartilage surfaces, composite layers of HA and LUB were grafted to Au surfaces and the antiadhesive properties were assessed using surface plasmon resonance and quartz crystal microbalance. A clear synergistic enhancement in antiadhesive properties was observed in the composite films relative to grafted HA and LUB layers alone. Atomic force microscopy (AFM) normal force measurements provide insight into the architecture of the HA/LUB composite layer and implicate a strong contribution of hydrophobic interactions in the binding of LUB end-domains directly to HA chains. These AFM force measurements indicate that the adhesion of LUB to HA is strong and indicate that the hydrophobic coupling of LUB to HA shields the hydrophobic domains in these molecules from interactions with other proteins or molecules.

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Lubricin as a novel nanostructured protein coating to reduce fibroblast density

Cited by 6 publications

References 14 publications

Structure and Property Changes in Self-Assembled Lubricin Layers Induced by Calcium Ion Interactions

Structure and Property Changes in Self-Assembled Lubricin Layers Induced by Calcium Ion Interactions

Two compartment pharmacokinetic model describes the intra‐articular delivery and retention of rhprg4 following ACL transection in the Yucatan mini pig

Interactions between Lubricin and Hyaluronic Acid Synergistically Enhance Antiadhesive Properties

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