Dataset Information

Effects of Hyaluronan Molecular Weight on the Lubrication of Cartilage-Emulating Boundary Layers.

ABSTRACT: Osteoarthritic joints contain lower-molecular-weight (MW) hyaluronan (hyaluronic acid, HA) than healthy joints. To understand the relevance of this HA size effect for joint lubrication, the friction and surface structure of cartilage-emulating surfaces with HA of different MWs were studied using a surface force balance (SFB) and atomic force microscopy (AFM). Gelatin (gel)-covered mica surfaces were coated with high-MW HA (HHA), medium-MW HA (MHA), or low-MW HA (LHA), and lipids of hydrogenated soy l-?-phosphatidylcholine (HSPC) in the form of small unilamellar vesicles, using a layer-by-layer assembly method. SFB results indicate that the gel-HHA-HSPC boundary layer provides very efficient lubrication, attributed to hydration lubrication at the phosphocholine headgroups exposed by the HA-attached lipids, with friction coefficients (COF) as low as 10-3-10-4 at contact stresses at least up to P = 120 atm. However, for the gel-MHA-HSPC and gel-LHA-HSPC surfaces, the friction, initially low, increases sharply at much lower pressures (up to 30-60 atm at most). This higher friction with the shorter chains may be due to their weaker total adhesion energy to the gelatin, where the attraction between the negatively charged HA and the weakly positively charged gelatin is attributed largely to counterion-release entropy. Thus, the complexes of LHA and MHA with the lubricating HSPC lipids are more easily removed by shear during sliding, especially at high stresses, than the HHA-HSPC complex, which is strongly adhered to gelatin. This is ultimately the reason for lower-pressure lubrication breakdown with the shorter polysaccharides. Our results provide molecular-level insight into why the decrease in HA molecular weight in osteoarthritic joints may be associated with higher friction at the articular cartilage surface, and may have relevance for treatments of osteoarthritis involving intra-articular HA injections.

SUBMITTER: Liu Z

PROVIDER: S-EPMC7556541 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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Effects of Hyaluronan Molecular Weight on the Lubrication of Cartilage-Emulating Boundary Layers.

Liu Zhang Z Lin Weifeng W Fan Yaxun Y Kampf Nir N Wang Yilin Y Klein Jacob J

Biomacromolecules 20200924 10

Osteoarthritic joints contain lower-molecular-weight (MW) hyaluronan (hyaluronic acid, HA) than healthy joints. To understand the relevance of this HA size effect for joint lubrication, the friction and surface structure of cartilage-emulating surfaces with HA of different MWs were studied using a surface force balance (SFB) and atomic force microscopy (AFM). Gelatin (gel)-covered mica surfaces were coated with high-MW HA (HHA), medium-MW HA (MHA), or low-MW HA (LHA), and lipids of hydrogenated ...[more]

PMID: 32931261

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Project description:ObjectiveTo compare equine synovial fluid (SF) from injured and control joints for cartilage boundary lubrication function; concentrations of the putative boundary lubricant molecules hyaluronan (HA), proteoglycan 4 (PRG4), and surface-active phospholipids (SAPLs); relationships between lubrication function and composition; and lubrication restoration by addition of HA.MethodsEquine SF from normal joints, joints with acute injury, and joints with chronic injury were analyzed for boundary lubrication of normal articular cartilage (kinetic friction coefficient [μ(kinetic) ]). Equine SF samples were analyzed for HA, PRG4, and SAPL concentrations and HA molecular weight distribution. The effect of the addition of HA, of different concentrations and molecular weight, on the μ(kinetic) of equine SF samples from normal joints and joints with acute injury was determined.ResultsThe μ(kinetic) of equine SF from joints with acute injury (0.036) was higher (+39%) than that of equine SF from normal joints (0.026). Compared to normal equine SF, SF from joints with acute injury had a lower HA concentration (-30%) of lower molecular weight forms, higher PRG4 concentration (+83%), and higher SAPL concentration (+144%). Equine SF from joints with chronic injury had μ(kinetic) , PRG4, and SAPL characteristics intermediate to those of equine SF from joints with acute injury and normal equine SF. Regression analysis revealed that the μ(kinetic) value decreased with increasing HA concentration in equine SF. The friction-reducing properties of HA alone improved with increasing concentration and molecular weight. The addition of high molecular weight HA (4,000 kd) to equine SF from joints with acute injury reduced the μ(kinetic) to a value near that of normal equine SF.ConclusionIn the acute postinjury stage, equine SF exhibits poor boundary lubrication properties, as indicated by a high μ(kinetic) . HA of diminished concentration and molecular weight may be the basis for this, and adding HA to deficient equine SF restored lubrication function.

Project description:We evaluated the mechanism by which high-molecular-weight hyaluronan (HMWH) attenuates nociceptor sensitization, in the setting of inflammation. HMWH attenuated mechanical hyperalgesia induced by the inflammatory mediator prostaglandin E2 (PGE2) in male and female rats. Intrathecal administration of an oligodeoxynucleotide antisense (AS-ODN) to mRNA for cluster of differentiation 44 (CD44), the cognate hyaluronan receptor, and intradermal administration of A5G27, a CD44 receptor antagonist, both attenuated antihyperalgesia induced by HMWH. In male rats, HMWH also signals via Toll-like receptor 4 (TLR4), and AS-ODN for TLR4 mRNA administered intrathecally, attenuated HMWH-induced antihyperalgesia. Since HMWH signaling is dependent on CD44 clustering in lipid rafts, we pretreated animals with methyl-β-cyclodextrin (MβCD), which disrupts lipid rafts. MβCD markedly attenuated HMWH-induced antihyperalgesia. Inhibitors for components of intracellular signaling pathways activated by CD44, including phospholipase C and phosphoinositide 3-kinase (PI3K), also attenuated HMWH-induced antihyperalgesia. Furthermore, in vitro application of HMWH attenuated PGE2-induced sensitization of tetrodotoxin-resistant sodium current, in small-diameter dorsal root ganglion neurons, an effect that was attenuated by a PI3K inhibitor. Our results indicate a central role of CD44 signaling in HMWH-induced antihyperalgesia and suggest novel therapeutic targets, downstream of CD44, for the treatment of pain generated by nociceptor sensitization.SIGNIFICANCE STATEMENT High-molecular-weight-hyaluronan (HMWH) is used to treat osteoarthritis and other pain syndromes. In this study we demonstrate that attenuation of inflammatory hyperalgesia by HMWH is mediated by its action at cluster of differentiation 44 (CD44) and activation of its downstream signaling pathways, including RhoGTPases (RhoA and Rac1), phospholipases (phospholipases Cε and Cγ1), and phosphoinositide 3-kinase, in nociceptors. These findings contribute to our understanding of the antihyperalgesic effect of HMWH and support the hypothesis that CD44 and its downstream signaling pathways represent novel therapeutic targets for the treatment of inflammatory pain.

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Dataset Information

Effects of Hyaluronan Molecular Weight on the Lubrication of Cartilage-Emulating Boundary Layers.

Publications

Effects of Hyaluronan Molecular Weight on the Lubrication of Cartilage-Emulating Boundary Layers.

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