Ganglioside GM3 Has an Essential Role in the Pathogenesis and Progression of Rheumatoid Arthritis

Rheumatoid arthritis (RA), a chronic systemic inflammatory disorder that principally attacks synovial joints, afflicts over 2 million people in the United States. Interleukin (IL)-17 is considered to be a master cytokine in chronic, destructive arthritis. Levels of the ganglioside GM3, one of the most primitive glycosphingolipids containing a sialic acid in the structure, are remarkably decreased in the synovium of patients with RA. Based on the increased cytokine secretions observed in in vitro experiments, GM3 might have an immunologic role. Here, to clarify the association between RA and GM3, we established a collagen-induced arthritis mouse model using the null mutation of the ganglioside GM3 synthase gene. GM3 deficiency exacerbated inflammatory arthritis in the mouse model of RA. In addition, disrupting GM3 induced T cell activation in vivo and promoted overproduction of the cytokines involved in RA. In contrast, the amount of the GM3 synthase gene transcript in the synovium was higher in patients with RA than in those with osteoarthritis. These findings indicate a crucial role for GM3 in the pathogenesis and progression of RA. Control of glycosphingolipids such as GM3 might therefore provide a novel therapeutic strategy for RA

Influence of differences in bone morphology on the distribution patterns of subchondral bone density across the trapeziometacarpal joint

We aimed to clarify the effects of morphological patterns of the trapezium and first metacarpal on the distribution of subchondral bone density across the articular surface of the trapeziometacarpal (TMC) joint using computed tomography osteoabsorptiometry. Thirty-three patients with normal TMC joints were evaluated. The percentages of the high-density areas in the radial-dorsal and ulnar-volar regions of the trapezium were significantly higher than that in the ulnar-dorsal region, and that of the ulnar-dorsal region of the first metacarpal was significantly lower than in the other three regions. The percentage of the high-density area of the radial-dorsal region of the trapezium and trapezial inclination (TI) showed a significant positive correlation, and the percentages of the high-density areas in the ulnar-dorsal and ulnar-volar regions had significant negative correlations with TI at the articular surface of the first metacarpal. These results indicate that bony morphologic differences in the trapezium affect the distribution pattern of subchondral bone density through the TMC joint

Ten years change in post-fracture care for hip fracture patients

IntroductionThis multicenter, retrospective study aimed to clarify the changes in postoperative care provided by orthopaedic surgeons after hip fractures and clarify the incidence of secondary fractures requiring surgery.Materials and methodsSubjects were patients with hip fracture treated surgically in seven hospitals during the 10-year period from January 2008 to December 2017. Data on patient demographics, comorbidities, preoperative and postoperative osteoporosis treatments, and secondary fractures were collected from the medical records.ResultsIn total, 4764 new hip fractures in 982 men and 3782 women (mean age: 81.310.0years) were identified. Approximately 10% of patients had a history of osteoporosis drug treatment and 35% of patients received postoperative drug treatment. The proportion of patients receiving postoperative drug therapy increased by approximately 10% between 2009 and 2010, 10% between 2010 and 2011, and 10% between 2011 and 2013. Although the rate of secondary fractures during the entire period and within 3years decreased from 2011, the rate of secondary fracture within 1year remained at around 2% every year.Conclusions p id=Par4 The approval of new osteoporosis drugs and the establishment of osteoporosis liaison services have had a positive effect on the use of postoperative drug therapy in the orthopedic field. Our finding that the rate of secondary fracture within 1year of the initial fracture remained around 2% every year, despite improvements in postoperative drug therapy, suggests that both rehabilitation for preventing falls and early postoperative drug therapy are essential to prevent secondary fractures

Clinical features related to GM3 in patients with RA or OA. A.

<p>Histology of RA and OA patients. Hematoxylin and eosin (HE) staining. Scale bars  = 200 µm. <b>B.</b> Quantification of total GSL glycans in human synovium (<i>n</i>  = 5 per group). <b>C.</b> Absolute and relative amounts of GM3 glycans in human synovium (<i>n</i>  = 5 per group). <b>D.</b> Quantification of GM3S mRNA in synovium and PBMCs in RA and OA patients (<i>n</i>  = 5 per group). Data shown are mean ± SEM. *<i>P</i><0.05, compared to OA patients.</p

Immune response of T cells in WT and GM3S^−/− mouse CIA models. A.

<p>CD4⁺, CD8⁺, B220⁺, and CD11b⁺ T cell contents of iLNs in WT and GM3S^−/− mice on day 7 after immunization with CII-CFA (<i>n</i>  = 3 per group). <b>B.</b> The Th17 cell content in CD4⁺ T cells in mouse iLNs (<i>n</i>  = 3 per group). Data shown are mean ± SEM. *<i>P</i><0.05, compared to WT mice.</p

Lactosylceramide (LacCer) is the key branching point of sphingolipid biosynthesis.

<p>In the synthetic pathway of sphingolipids, four alternate pathways (lacto-series, neolacto-series, globo-series, and isoglobo-series) branch-off from LacCer. GM3S^−/− mice, in which the GM3 synthase gene is disrupted, produced only o-series gangliosides, including GA2 and GA1, and not a-series or b-series gangliosides.</p