This article has an associated First Person interview with the first author of the paper. By facilitating insertion of TMDs that permit essential mammalian sterol-regulating enzymes to mature accurately, the EMC is an important biogenic determinant of cellular robustness to fluctuations in cholesterol availability.
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Insertion of the weakly hydrophobic tail-anchor (TA) of SQS into the ER membrane by the EMC ensures sufficient flux through the sterol biosynthetic pathway while biogenesis of polytopic SOAT1 promoted by the EMC provides cells with the ability to store free cholesterol as inert cholesteryl esters. Lipidomic and proteomic analyses revealed defective biogenesis and concomitant loss of the TMD-containing ER-resident enzymes sterol-O-acyltransferase 1 (SOAT1) and squalene synthase (SQS, also known as FDFT1), which serve strategic roles in the adaptation of cells to changes in cholesterol availability. We report that EMC deficiency limits the cellular boundaries defining cholesterol tolerance, reflected by diminished viability with limiting or excessive extracellular cholesterol. The ER membrane protein complex (EMC) is a newly described transmembrane domain (TMD) insertase linked with various phenotypes, but whose clients and cellular responsibilities remain incompletely understood. The study also emphasised the significance of these findings given increasing life expectancy, the resulting structural changes in the human population and the comorbidities aggravated by immobility due to pain.Īs such, the authors present the potential of the ESM eggshell membrane nutraceutical as a more secure option to analgesics and non-steroidal, anti-inflammatory drugs (NSAIDS) “that have shown limited effectiveness and have induced several multiorgan toxicities.The eukaryotic endoplasmic reticulum (ER) membrane contains essential complexes that oversee protein biogenesis and lipid metabolism, impacting nearly all aspects of cell physiology. “Moreover, our results also indicate a dose-dependent response, which should be taken into account for later use in therapeutics to establish the correct dosage.” “This study reports an improvement in all of the variables monitored in those subjects who were consuming eggshell membrane, most likely resulting from physiological changes in the musculature associated with the amelioration of knee functionality and a better quality of life due to a reduction in perceived pain,” the study concluded.
OutcomesĪll groups showed a significant decrease in pain perception, the study found, but the high-dose group reported maximum values, in addition to significant increase in muscle strength and sleep quality compared to the other two groups.
The study also evaluated secondary outcome variables including knee functional ability using the Western Ontario and McMaster Universities Osteoarthritis (WOMAC) questionnaire, quadriceps muscle strength assessed by isometric and isokinetic trials, and quality of sleep measured using the Pittsburgh Sleep Quality Index. “The primary outcome variable was knee pain which was assessed using a visual analogue scale (VAS) of 10 cm, defining extreme limits such as ‘no pain at all’ and ‘pain as bad as it could be’,” the authors explained.
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A third group received a placebo control of maltodextrin, and all 75 participants who completed the trial were previously diagnosed with osteoarthritis and chronic knee pain. The randomised, controlled, double-blind, single centre clinical trial consisted of once-daily oral ingestion of a low-dose of 300 mg or a high-dose of 500 mg of the eggshell membrane to two groups over an eight-week test period. It is registered under the ESM, membraflex, membrapet, membraderm and membrasport trademarks. The 100% natural supplement produced from eggs from caged hens is primarily composed of fibrous collagen proteins, smaller percentages of glycosaminoglycans and hexosamine, as well as significant amounts of hyaluronic acid. The study was carried out at the UCAM Catholic University of Murcia in Spain and was sponsored by Spanish manufacturer Torolis Explotaciones, which provided the eggshell membrane study product. “Such a variable set extends the findings of previous studies that have already observed changes in the functionality of knee joints by measuring the range of motion.” “Here, for the first time, two quantitative variables (mobility and strength of knee joint), as well as qualitative ones (pain, functional ability, and sleep quality), were monitored to accurately evaluate changes in the quality of life of subjects affected by this common pathology,” the authors of the study stated.
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