Collagen I and various proteoglycans contribute

Collagen I and various proteoglycans contribute to the tensile strength and viscoelastic properties of the tendon tissue, respectively (Puxkandl et al., 2002; Robinson et al., 2004). Furthermore, proteoglycans and cross-linking MK-2206 Supplier modulate collagen I fibrillogenesis during rest and training (Kalamajski and Oldberg, 2010; Kwansa et al., 2014). Therefore, we last examined what effect Tnmd exerts on cross-linker genes in resting and exercise conditions. Comparison of mRNA levels of cross-linkers in tendons of WT mice revealed only one significant exercise-responder gene - lysyl hydroxylase. In contrast, the tendons of the mutant mice exhibited a very different molecular response to exercise: namely all genes that were significantly downregulated in sedentary animals responded by upregulation in the trained. The expression of the extracellular collagen cross-linker gene Lox was augmented in the KO mice as a result of exercise. Heinemeier et al. (2007) have shown Lox upregulation in rat tendon with increased loading, which is suggested to potentiate the tendon collagen cross-linking process. At the protein level, we observed discrepancies in the expression profile, a phenomenon similar to that seen in the development of early osteoarthritis in articular cartilage: comparison between osteoarthritic versus healthy patients revealed that link protein, among several other genes, increased 50-fold at the mRNA level compared with only a three-fold increase at the protein level in the cartilage of diseased donors (Cs-Szabo et al., 1997). At present, how Tnmd exactly regulates collagen I fibrillogenesis remains difficult to decipher due to our lack of understanding of Tnmd signaling pathways. Our data greatly emphasize the need for future studies to accurately explain the signaling pathways of this gene protein.
Funding Sources German Research Foundation, D.D. grant Nr. DO1414/3-1.
Conflict of Interest
Author Contributions
Acknowledgments D.D. acknowledges the support of the German Research Foundation (DO1414/3-1). TS, SB and HCS acknowledge the support through the CANTER research focal point of the Bavarian State Ministry for Science and Education. The funders were not involved in study design, data collection, data analysis, interpretation and writing of the report. We thank Martina Burggraf for technical assistance in generating data for Fig. 1.
Introduction The bacteria that colonise newborn mammals contribute to health and disease in numerous ways (Deshmukh et al., 2014). The early pattern of development of the microbiome in infants nursed in intensive care has been linked with serious consequences including the development of neonatal necrotising enterocolitis (NEC) (Morowitz et al., 2010). NEC has a high associated mortality and morbidity and is the most common serious gastro-intestinal complication of prematurity with an incidence of between 6% to 10% in babies <1500g birthweight (Lin and Stoll, 2006). Microbial diversity is characteristically reduced in infants at risk of developing NEC (Wang et al., 2009) leading to the proposition that the inflammatory response of the gut to an abnormal pattern of early microbial colonisation may underlie the pathogenesis of NEC (Neu and Walkerm, 2011). Consequently the administration of ‘beneficial’ live bacteria in the form of probiotics could help prevent NEC. The demonstration that probiotics reduce the risk of severe NEC in preterm infants supports this view, although such a reduction appears dependent on the infant\'s birthweight and the bacterial strain used (Aceti et al., 2015; AlFaleh and Anabrees, 2014). Mechanisms by which probiotics might prevent NEC include the possibility that they modify the composition, and increase the stability and diversity of gastrointestinal microbial populations (AlFaleh and Anabrees, 2014). However, the results of studies exploring the role of probiotics on the preterm gut and NEC incidence are confounded by small sample numbers and methodological inconsistencies (Aceti et al., 2015). Additionally, placebo controlled probiotic trials in infants have often omitted a comparison between the microbial composition of the two groups and subsequently do not allow a full understanding of the impact, if any, of probiotic administration on the developing microbiome.