The skeletal phenotype of chondroadherin deficient mice

Chondroadherin, a leucine rich repeat extracellular matrix protein with functions in cell to matrix interactions, binds cells via their a2b1 integrin as well as via cell surface proteoglycans, providing for different sets of signals to the cell. Additionally, the protein acts as an anchor to the matrix by binding tightly to collagens type I and II as well as type VI. We generated mice with inactivated chondroadherin gene to provide integrated studies of the role of the protein. The null mice presented distinct phenotypes with affected cartilage as well as bone. At 3–6 weeks of age the epiphyseal growth plate was widened most pronounced in the proliferative zone. The proteome of the femoral head articular cartilage at 4 months of age showed some distinct differences, with increased deposition of cartilage intermediate layer protein 1 and fibronectin in the chondroadherin deficient mice, more pronounced in the female. Other proteins show decreased levels in the deficient mice, particularly pronounced for matrilin-1, thrombospondin-1 and notably the members of the a1-antitrypsin family of proteinase inhibitors as well as for a member of the bone morphogenetic protein growth factor family. Thus, cartilage homeostasis is distinctly altered. The bone phenotype was expressed in several ways. The number of bone sialoprotein mRNA expressing cells in the proximal tibial metaphysic was decreased and the osteoid surface was increased possibly indicating a change in mineral metabolism. Micro-CT revealed lower cortical thickness and increased structure model index, i.e. the amount of plates and rods composing the bone trabeculas. The structural changes were paralleled by loss of function, where the null mice showed lower femoral neck failure load and tibial strength during mechanical testing at 4 months of age. The skeletal phenotype points at a role for chondroadherin in both bone and cartilage homeostasis, however, without leading to altered longitudinal growth

Only an integrated approach across academia, enterprise, governments, and global agencies can tackle the public health impact of climate change

Background: Despite considerable global attention to the issues of climate change, relatively little priority has been given to the likely effects on human health of current and future changes in the global climate. We identify three major societal determinants that influence the impact of climate change on human health, namely the application of scholarship and knowledge; economic and commercial considerations; and actions of governments and global agencies. Discussion: The three major areas are each discussed in terms of the ways in which they facilitate and frustrate attempts to protect human health from the effects of climate change. Academia still pays very little attention to the effects of climate on health in poorer countries. Enterprise is starting to recognise that healthy commerce depends on healthy people, and so climate change presents long-term threats if it compromises health. Governments and international agencies are very active, but often face immovable vested interests in other sectors. Overall, there tends to be too little interaction between the three areas, and this means that potential synergies and co-benefits are not always realised. Conclusion: More attention from academia, enterprise, and international agencies needs to be given to the potential threats the climate change presents to human health. However, there needs to also be much closer collaboration between all three areas in order to capitalise on possible synergies that can be achieved between them

Micrographs of the epiphyseal plate in CHAD −/− and WT mice.

<p>Light micrographs of CHAD−/− (2a) and WT (2b) mice at 3 weeks of age. A small but significant increase in the height of the growth plate mostly confined to the proliferative zone was confirmed by histomorphometry (<a href="http://www.plosone.org/article/info:doi/10.1371/journal.pone.0063080#pone-0063080-t003" target="_blank">table 3</a>). Epon-embedded tissue, toluidine blue staining (x 20).</p

Micro-CT cortical/trabecular bone parameters in 4 month old mice.

<p>Micro-CT cortical/trabecular bone parameters in 4 month old mice.</p

Ultrastructural distribution of OPN and BSP in bone of CHAD−/− and WT mice.

<p>Ultrastructural distribution of OPN and BSP in bone of CHAD−/− and WT mice.</p

Changes in the proteome of cartilage from mice with the CHAD gene inactivated.

<p>Changes in the proteome of cartilage from mice with the CHAD gene inactivated.</p