Effect of n-3 PUFA on extracellular matrix protein turnover in patients with psoriatic arthritis: a randomized, double-blind, placebo-controlled trial

Psoriatic arthritis (PsA) is a chronic inflammatory disease characterized by involvement of skin, axial and peripheral skeleton. An altered balance between extracellular matrix (ECM) formation and breakdown is a key event in PsA, and changes in ECM protein metabolites may provide insight to tissue changes. Dietary fish oils (n-3 PUFA) might affect the inflammation driven tissue turnover. The aim was to evaluate ECM metabolites in patients with PsA compared to healthy individuals and investigate the effects of n-3 PUFA. The 24-week randomized, double-blind, placebo-controlled trial of PUFA included 142 patients with PsA. Fifty-seven healthy individuals were included for comparison. This study is a sub-study investigating biomarkers of tissue remodelling as secondary outcomes. Serum samples at baseline and 24 weeks and healthy individuals were obtained, while a panel of ECM metabolites reflecting bone and soft tissue turnover were measured by ELISAs: PRO-C1, PRO-C3, PRO-C4, C1M, C3M, C4M, CTX-I and Osteocalcin (OC). C1M, PRO-C3, PRO-C4 and C4M was found to be elevated in PsA patients compared to the healthy individuals (from 56 to 792%, all p < 0.0001), where no differences were found for OC, CTX-I, PRO-C1 and C3M. PRO-C3 was increased by 7% in patients receiving n-3 PUFA after 24 weeks compared to baseline levels (p = 0.002). None of the other biomarkers was changed with n-3 PUFA treatment. This indicates that tissue turnover is increased in PsA patients compared to healthy individuals, while n-3 PUFA treatment for 24 weeks did not have an effect on tissue turnover. Trial registration NCT01818804. Registered 27 March 2013–Completed 18 February 2016. https://clinicaltrials.gov/ct2/show/NCT01818804?term=NCT01818804&rank=1

Strontium Uptake and Intra-Population 87Sr/86Sr Variability of Bones and Teeth—Controlled Feeding Experiments With Rodents (Rattus norvegicus, Cavia porcellus)

Strontium isotopes in biogenic apatite, especially enamel, are widely employed to determine provenance and track migration in palaeontology and archaeology. Body tissues record the 87Sr/86Sr of bioavailable Sr of ingested food and water. To identify non-local individuals, knowledge of the 87Sr/86Sr of a non-migratory population is required. However, varying factors such as tissue turnover rates, feeding selectivity, Sr content, digestibility of food, and the ingestion of mineral dust can influence body tissue 87Sr/86Sr. To evaluate the Sr contribution of diet and water to mammalian hard tissues 87Sr/86Sr, controlled feeding studies are necessary. Here we present 87Sr/86Sr from controlled feeding experiments with two rodent species (Rattus norvegicus, Cavia porcellus). Due to the continuous and fast incremental growth of rat and guinea pig incisors (~0.1 – 0.5 mm/day), their enamel is expected to record isotopic dietary changes. For Experiment-1: Diet Switch, animals were switched from their respective supplier food to a pelleted experimental diet containing either insect-, plant-, or meat-meal and a staggered-sampling approach was used to monitor the 87Sr/86Sr changes in rat incisor enamel and bone over the course of the experiment. In Experiment-2: Basic Diets, separated cohorts (n = 6) of rats and guinea pigs were fed one of the three pelleted diets and received tap water for 54 days. While the rat incisors showed a complete tissue turnover, the slower-growing guinea pig incisors partially retained supplier diet-related isotopic compositions. In addition, one group of rats fed plant-meal pellets received Sr-rich mineral water, demonstrating that drinking water can be an important Sr source in addition to diet. Additionally, a leaching experiment showed that only a small fraction of diet-related Sr is bioavailable. Finally, in Experiment-3: Dust Addition, guinea pigs were fed pellets with and without addition of 4% of isotopically distinct dust (loess or kaolin). Animals that received kaolin-containing pellets displayed increased enamel 87Sr/86Sr. Intra-population 87Sr/86Sr variability within each feeding group was small and thus we conclude that it should not affect interpretations of 87Sr/86Sr in provenance studies. However, the differences between bulk food and leachate 87Sr/86Sr highlight the importance of Sr bioavailability for provenance studies and Sr isoscapes.