NO regulates aggrecanase activity at a post-transcriptional level in response to TNF-alpha treatment while having no effect on IL-1beta treated cartilage explants.

Objective To determine changes in chondrocyte transcription of a range of anabolic, catabolic and signaling genes following simultaneous treatment of cartilage with IGF-1 and ramp-and-hold mechanical compression, and compare with effects on biosynthesis. Methods Explant disks of bovine calf cartilage were slowly compressed (unconfined) over 3-min to their 1mm cut-thickness (0%-compression) or to 50%-compression with or without 300 ng/ml IGF-1. Expression of 24 genes involved in cartilage homeostasis was measured using qPCR at 2, 8, 24, 32, 48 hours after compression ± IGF-1. Clustering analysis was used to identify groups of co-expressed genes to further elucidate mechanistic pathways. Results IGF-1 alone stimulated gene expression of aggrecan and collagen II, but simultaneous 24-hour compression suppressed this effect. Compression alone upregulated expression of MMP-3, MMP-13, ADAMTS-5 and TGF-β, an effect not reversed by simultaneous IGF-1 treatment. Temporal changes in expression following IGF-1 treatment were generally slower than that following compression. Clustering analysis revealed five distinct groups within which the pairings, TIMP-3 and ADAMTS-5, MMP-1 and IGF-2, and IGF-1 and Collagen II, were all robustly co-expressed, suggesting inherent regulation and feedback in chondrocyte gene expression. While aggrecan synthesis was transcriptionally regulated by IGF-1, inhibition of aggrecan synthesis by sustained compression appeared post-transcriptionally regulated. Conclusion Sustained compression markedly altered the effects of IGF-1 on expression of genes involved in cartilage homeostasis, while IGF-1 was largely unable to moderate the transcriptional effects of compression alone. The demonstrated co-expressed gene pairings suggest a balance of anabolic and catabolic activity following simultaneous mechanical and growth factor stimuli.

Purpose Cigarette smoking in the perinatal period is associated with costly morbidity and mortality for mother and infant, yet many women continue to smoke throughout their pregnancy and following delivery. This report describes tobacco use prevalence among perinatal smokers identified through an “opt-out” inpatient smoking cessation clinical service. Description Adult women admitted to the peripartum, delivery, and postpartum units at a large academic hospital were screened for tobacco use. Smokers were identified through their medical record and referred to a bedside consult and follow-up using an interactive voice response (IVR) system to assess smoking up to 30 days post-discharge. Assessment Between February 2014 and March 2016, 533 (10%) current and 898 (16%) former smokers were identified out of 5649 women admitted to the perinatal units. Current smokers reported an average of 11 cigarettes per day for approximately 12 years. Only 10% reported having made a quit attempt in the past year. The majority of smokers (56%) were visited by a bedside tobacco cessation counselor during their stay and 27% were contacted through the IVR system. Those counselled in the hospital were twice as likely (RR=1.98, CI=1.04–3.78) to be abstinent from smoking using intent-to-treat analysis at any time during the 30 days post-discharge. Conclusions This opt-out service reached a highly nicotine-dependent perinatal population, many of whom were receptive to the service, and it appeared to improve abstinence rates postdischarge. Opt-out tobacco cessation services may have a significant impact on the health outcomes of this population and their children.

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