CONGRESS REPORT
BASIC/TRANSLATIONAL SCIENCE
Anna Teti
The 2012 ECTS meeting held in Stockholm provided attendees with detailed up-to-date information on
various important aspects of bone biology, with great translational interaction and a look at the clinical
impact of new discoveries.
In the 6 Symposia and 3 Workshops which focused on basic/translational science, we learned about
cutting-edge and revolutionary new findings that are likely to improve knowledge on the involvement of
the skeleton in various human diseases. For instance, the pharmacology of the purinergic receptors in bone
cells described in Symposium 1 provided a link between these receptors and matrix mineralization, as well
as between mechanotransduction and bone metabolism. This data suggests that purinergic receptor
agonists and antagonists could be important tools to regulate bone function and therefore could be
foreseen as important determinants for future pharmacological developments.
Symposium 2 addressed the, yet to be fully understood, issue of bone matrix mineralization with a good
mix between general concepts of matrix mineralization in vertebrates and description of relevant molecular
regulators, especially the members of the SIBLING protein family whichcould also play a role in pathological
ectopic mineralization, for instance in the blood vessel wall. Although the matrix vesicles involved in the
process were discovered years ago, understanding the underlying molecular mechanisms represents an
important goal for future research. Very importantly, Symposium 3, focused on the RANKL pathway, made
a point about the multitude of activities that this cytokine accomplishes not only in bone but also in the
regulation of the immune system, in breast development, in the induction of mammary cancer and in the
control of body temperature. While these biological aspects may open new perspectives for understanding
the pathogenesis of various diseases, they may represent consistent concerns for the use of anti-RANKL
therapy. The Symposium touched on the clinical effects of RANKL antagonists describing pros and cons with
an objective comparison with other antiresorptive drugs.
In Symposium 4 we heard new and important observations on the role of the until recently believed to be
solely an osteoclast-specific gene, TCIGR1, in gastric acidification and calcium absorption. This was a good
example of a genetic disease, osteopetrosis, which opened new perspectives for other diseases due to
impairment of gastric acidification, such as the hypochlorydia, which largely affects the aging population.
The observation has important diagnostic implications since, due to the poor calcium intake, the
osteopetrotic patients affected by TCIGR1 gene mutations present histopathologically with an osteopetrorickets(malacia) instead of a frank osteopetrosis. There are also consequences for therapy because in the
case of impaired gastric acidification, calcium should be supplemented as calcium gluconate because of its
higher solubility at less acidic pH. Again this Symposium represented an excellent mix of basic, translational
and clinical science as it ended up with an interesting epidemiological analysis showing pros and cons of the
evaluation of large databases.
Symposium 5 reported an impressive set of data on the role of nitric oxide in bone, focusing on two aspects
of bone biology: the mechanical adaptation of bone and the effects of the organic nitrates in osteoporosis.
Again this was an excellent intersection between basic and clinical science and revealed how dramatically
complicated is the metabolism of this free radical involved in the regulation of many biological processes.
This symposium focussed attention on the osteocytes, as they are essential regulators of
mechanotrasdution in bone, also rapidly producing nitric oxide in response to mechanical forces.
Finally, Symposium 6 addressed the problem of senescence, both from a general point of view and
specifically regarding bone metabolism. Very nicely, senescence was described as a mechanism adopted by
cells to defend themselves from malignancy, protecting organisms from developing tumors early in life, but
causing pathological alterations later on. Not surprisingly, osteoporosis has been depicted as a typical
consequence of senescence.
Workshop 1 provided outstanding examples of new technical developments that could greatly affect the
bone field. Excellent lectures focusing on pluripotent stem cell tools, green fluorescent protein reporters
and innovative zinc-finger mediated transgenic models were delivered, with wonderful iconographic
presentations and ample discussion. This workshop was very much appreciated by new investigators who
now know that future technical development will greatly help them to be creative and ground-breaking.
Workshop 3 focused on the NF-κB signaling, which is so important in bone cell biology, also causing a tight
association with inflammatory diseases. We heard the link of this pathway with Paget’s disease of bone,
and learned how the NF-κB signal not only regulates bone resorption through the RANKL pathway, but also
bone formation, via an increase of JNK and Fra-1 expression.
Finally, Workshop 5 addressed important new developments in protein processing which explain how
alterations of their handling can correlate with pathologies. For instance, unfolded protein response has
been described in chondrodysplasia with mechanisms affecting endochondral ossification, while alterations
of proteocatabolic pathways are associated with multiple myeloma and damages in autophagy can
contribute to the pathogenesis of osteoporosis. All this information translationally fuels the clinical field
because pharmacological treatments, currently used or being developed, are based on these notions
providing another good example on the interaction between basic and clinical sciences.
The Symposia and Workshops were the frames for the ongoing scientific work presented in the oral and
poster sessions, especially by new investigators. This is a major strength of the ECTS meetings which has
well developed new investigator seminar, fully organized and chaired by the new investigator committee
members of the ECTS. It is nice that established scientists feel welcome guests to this seminar, which
however stands alone thanks to the excellent work of talented and motivated ECTS young people. Excellent
indeed!