Changing views

Rather than look ahead and anticipate what you are all going to say over the next couple of days, let me look back at the last Novartis Foundation Symposium (or

Ciba Foundation, as it was then known) that was held on this topic in 1988, entitled the 'Cell and molecular biology of vertebrate hard tissues'. It had a very heated discussion section. It is interesting to see what the aim of this meeting was, as a way of illustrating the difficulty of trying to predict how a field is going to change. In his introduction, Gideon Rodan says, 'In last few years we have seen considerable advances in identifying molecules that are part of the extracellular matrix. Our discussion will focus on their biochemical characterization, their structure, the interaction of these molecules with cells and with other similar molecules, and the regulation of their production and degradation' (Rodan 1988, p 1). The emphasis was on the extracellular matrix as the controlling element of skeletogenesis. We are not talking about the extracellular matrix in this context at this meeting at all—we're talking about cells and what's happening at the cell surface. So there has been a major shift in emphasis away from the extracellular matrix as containing the control, to the cells. This was identified by Melvyn Glimcher in the final general discussion to the 1988 meeting, where he said, 'To sum up, we need a greater understanding of the complex system of cell—cell and cell—matrix systems of communication and other factors which regulate cell proliferation and differentiation to specific cell types, so that we can tailor the repair and healing process for different types of bony tissue, in order to achieve the regulation of bone cell populations and formation to fit the specific task of repair at hand' (Ciba Foundation 1988, p 280). This could stand as a summary of the proposal that Adam Wilkins and Gillian Morriss-Kay have put together for this meeting, with the emphasis on cell—cell interactions.

Under the heading of 'Future perspectives', H. Fleisch said, 'We should take advantage of the knowledge developed in the haemopoietic field, on the development from stem cells to mature blood cells, and we should investigate whether a cascade of factors is necessary in bone differentiation from stem cells to bone-forming cells' (Ciba Foundation 1988, p 288—289). Clearly, a lot of the present meeting is going to be about those cascades of factors which are involved in going from stem cell to bone-forming cell, with major advances in identifying the cascades of molecules that are involved at each of the steps I have outlined.

We have made much less progress on the topic that was raised by J. D. Termine in 1988: 'Over the next few years the definition of the lineage of osteoblast phenotype should be achieved at the molecular level' (Ciba Foundation 1988, p288). I don't think we're quite there yet. Continuing Termine's conclusion: 'The big task for this group, and the field as a whole, is to develop in vitro systems of bone resorption and bone formation that more accurately reflect what's going on in the adult Presently our techniques are basically bone modelling ones, based on embryos or neonates' (Ciba Foundation 1988, p 289—290). I think this is still a major issue: how well can we model what's happening in the adult, with studies based on systems that are derived from embryos and neonates?

With this brief outline of skeletogenesis, I would now like to introduce the first paper.

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