8. Interactions of osteotropic influences

The purpose of presenting the previous account of cytokine and eicosanoid actions is to illustrate the complexity of the control of bone and chondrocyte metabolism. It is unfortunate that experiments to determine the effects of cytokines produce such conflicting results in apparently similar but not identical conditions. However, this shows that the control of bone growth and remodelling is effected by a tightly regulated and highly specific sequence of ordered changes in expression of cytokines (Suva et al., 1993). This is not the sole manner of regulation of action of osteotropic agents. Modulation of receptors and inhibitors is a critical and important stage of regulation of action, which can completely reverse the effects of a given stimulus. The inhibitor for IL-1 is a normal circulating modulator of the actions of IL-1 (Seckinger et al., 1990), and its absence is capable of upregulating resorption or other effects of IL-1. Other inhibitors of cytokine actions include fragments of their receptors shed from cells, which bind the ligand without eliciting cellular responses.

Even after ligand receptor binding, there are many levels at which regulation of action is possible. Immediate intracellular consequences of binding such as tyrosine kinase activation, and proto-oncogene expression are both complex processes which involve many steps dependent on other processes within the cell. Even if all these actions occur, it is possible to express messenger RNA which will not be transcribed into protein, or protein which will either not be secreted, or which will be inhibited.

The effects of inflammation on bone growth are therefore hard to predict accurately, as the inflammatory process is one which involves changes in many agents with osteotropic actions. It is rare that any of these agents stimulate any long-term gain in bone length which is reflected in an increase in adult height, so the likely effect of inflammation is to reduce bone length, by a combination of systemic and local disturbances of normal growth.