Early Tissue Development Research Articles

Vitamin A: A Key Inhibitor of Adipocyte Differentiation.

Inhibiting adipocyte differentiation, the conversion of preadipocytes to mature functional adipocytes, might represent a new approach to treating obesity and related metabolic disorders. Peroxisome proliferator-activated receptor γ and CCAAT-enhancer-binding protein α are two master coregulators controlling adipogenesis both in culture and in vivo. Many recent studies have confirmed the relationship between retinoic acid (RA) and the conversion of embryonic stem cells into adipocytes; however, these studies have shown that RA potently blocks the differentiation of preadipocytes into mature adipocytes. Nevertheless, the functional role of RA in early tissue development and stem cell differentiation, including in adipose tissue, remains unclear. This study highlights transcription factors that block adipocyte differentiation and maintain preadipocyte status, focusing on those controlled by RA. However, some of these novel adipogenesis inhibitors have not been validated in vivo, and their mechanisms of action require further clarification.

Genomics and Successful Aging: Grounds for Renewed Optimism?

Successful aging depends in part on delaying age-related disease onsets until later in life. Conditions including coronary artery disease, Alzheimer's disease, prostate cancer, and type 2 diabetes are moderately heritable. Genome-wide association studies have identified many risk associated single-nucleotide polymorphisms for these conditions, but much heritability remains unaccounted for. Nevertheless, a great deal is being learned. Here, we review age-related disease associated single-nucleotide polymorphisms and identify key underlying pathways including lipid handling, specific immune processes, early tissue development, and cell cycle control. Most age-related disease associated single-nucleotide polymorphisms do not affect coding regions of genes or protein makeup but instead influence regulation of gene expression. Recent evidence indicates that evolution of gene regulatory sites is fundamental to interspecies differences. Animal models relevant to human aging may therefore need to focus more on gene regulation rather than testing major disruptions to fundamental pathway genes. Recent larger scale human studies of in vivo genome-wide expression (notably from the InCHIANTI aging study) have identified changes in splicing, the "fine tuning" of protein sequences, as a potentially important factor in decline of cellular function with age. Studies of expression with muscle strength and cognition have shown striking concordance with certain mice models of muscle repair and beta-amyloid phagocytosis respectively. The emerging clearer picture of the genetic architecture of age-related diseases in humans is providing new insights into the underlying pathophysiological pathways involved. Translation of genomics into new approaches to prevention, tests and treatments to extend successful aging is therefore likely in the coming decades.

Effect of hyaluronan on calcification-nodule formation from human periodontal ligament cell culture.

The periodontal ligament (PDL) has been found to house progenitor elements which may give rise to a new periodontium when properly triggered. Complex molecular mechanisms are involved in guiding such cells towards their final regenerative task. Hyaluronan (HA), an extracellular matrix molecule abundantly present during early tissue development, is usually found at high concentrations in all adult mammalian PDL tissue. In this study, PDL cells were cultured on HA coated experimental plastic Petri's dishes (E.D.) and mineralized-nodules formation, at the microscopical level, was evaluated in comparison to HA-free control dishes (C.D.) after 21 days. Little colony formation occurred in presence of HA, whereas CD showed normal cell confluence with mineralization of nodules even at 10 days. However, when harvesting was performed from both dishes after only 12 hours, before cell aggregation occurred, cell confluence and nodule formation could be seen with no apparent difference between test and control. This study shows that, with respect to PDL cells, hyaluronan seems to inhibit cell adhesion, although with no interference with cell aggregates calcifying potentials. This latter finding may: a) provide further insight in analyzing the properties of extracellular matrix substrates in the PDL environment, b)guide research to possible explanations on how the PDL maintains its characteristics of uncalcified tissue and c) lead to theorize regarding utilization in tissue regeneration. (Journal of Applied Biomaterial & Biomechanics 2003; 1: 84-90).