Dataset Information

Comparative Study on Hyaluronic Acid Binding to Murine SAA1.1 and SAA2.2.

ABSTRACT: Persistently high plasma levels of serum amyloid A (SAA) may induce AA amyloidosis in various organs causing their dysfunction. Although SAA isoforms share a high degree of homology, only the SAA1.1 isoform is found in amyloid deposits. SAA1.1 misfolding is a nucleation-dependent process with dimer and trimer formation playing a major role in SAA fibril formation through self-catalyzed recruitment of native SAA molecules. Yet, a structural model of initial SAA oligomerization is still missing. In this study, we constructed a loosely associated model for murine SAA1.1 and SAA2.2 dimers in the presence or absence of hyaluronic acid as an exemplary glycosaminoglycan, a factor known to facilitate SAA fibril formation. Molecular dynamics simulations predicted that hyaluronic acid finally stabilized in a different binding pocket of the pathogenic SAA1.1 dimer compared to the nonpathogenic SAA2.2 dimer. Besides, Markov state modeling points to dynamic behavioral differences between the linker region of SAA1.1 and SAA2.2 and identifies a state unique to pathogenic SAA1.1 while bound to hyaluronic acid. The presence or absence of hyaluronic acid, as well as the dimer interface switch, affects dynamic behavior and possible oligomeric states, proposing a conceivable clue to the deviant pathogenicity of the two SAA isoforms.

SUBMITTER: Jin L

PROVIDER: S-EPMC6704436 | biostudies-literature | 2019 Aug

REPOSITORIES: biostudies-literature

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Comparative Study on Hyaluronic Acid Binding to Murine SAA1.1 and SAA2.2.

Jin Lu L Syrovets Tatiana T Scheller Judith S JS Zhang Xinlei X Simmet Thomas T

ACS omega 20190806 8

Persistently high plasma levels of serum amyloid A (SAA) may induce AA amyloidosis in various organs causing their dysfunction. Although SAA isoforms share a high degree of homology, only the SAA1.1 isoform is found in amyloid deposits. SAA1.1 misfolding is a nucleation-dependent process with dimer and trimer formation playing a major role in SAA fibril formation through self-catalyzed recruitment of native SAA molecules. Yet, a structural model of initial SAA oligomerization is still missing. I ...[more]

PMID: 31460467

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Project description:Osteoarthritis (OA) of the trapeziometacarpal joint (TMJ) is a disabling condition with a significant impact on quality of life. The optimal management of hand OA requires a combination of non-pharmacological and pharmacological treatments that include intra-articular (i.a.) therapy. EULAR experts recommend corticosteroid injections in TMJ OA and underline the usefulness of hyaluronic acid (HA). The aim of this study was the assessment of the efficacy and tolerability of i.a. injections of a hybrid formulation of HA (Sinovial H-L®) in comparison to triamcinolone in patients with TMJ OA.This 6-months observational comparative study, retrospective analyzed the medical records of 100 patients with monolateral or bilateral TMJ OA, treated with two injections of Sinovial H-L® (Sinovial H-L Group) or of triamcinolone acetonide (Triamcinolone Group). Clinical assessments were recorded at the time of the first and second injection and after one, 3 and 6 months. The primary outcomes were the change in global pain on a Visual Analogue Scale (VAS) and in hand function evaluated by the Functional Index for Hand OA (FIHOA) from baseline to month 6. Secondary outcomes were the improvement of the duration of morning stiffness, Health Assessment Questionnaire (HAQ) and the Medical Outcomes Study 36-Item Short Form (SF-36). The comparison between the two groups of treatment were performed with the Wilcoxon rank-sum test for continuous variables and with chi-square or Fisher exact test for categorical variables. Statistical significance was set at p?<?0.05.Both therapies provided effective pain relief and joint function improvement, but the benefits achieved were statistically significantly superior in the Sinovial H-L Group than the Triamcinolone Group after one month (p?<?0.01) from the beginning of the therapy and during the 6-months follow-up (p?<?0.001). Furthermore, Sinovial H-L® was associated with a significant decrease in the duration of morning stiffness and with a significant improvement in the HAQ score and physical component summary (PCS)-SF-36.Our results suggested that the hybrid formulation of HA may be more effective than triamcinolone in pain relief and joint function improvement with a rapid and persistent effect, resulting a valid alternative to steroid in the management of TMJ OA.ClinicalTrials.gov, date of registration: June 14, 2017, NCT03200886 . The present trial was retrospectively registered.

Dataset Information

Comparative Study on Hyaluronic Acid Binding to Murine SAA1.1 and SAA2.2.

Publications

Comparative Study on Hyaluronic Acid Binding to Murine SAA1.1 and SAA2.2.

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