During physiological and pathological skeletal remodelling, immune cells and stromal fibroblasts near active bone-forming and bone-resorbing surfaces might modulate the functions of skeletal tissue cells. Osteoblasts, osteoclasts and their progenitor cells are the probable direct targets of these effector cells (e.g. lymphocytes and monocytes) which act through direct contact or the release of soluble ligands (e.g. interleukin 1 or tumour necrosis factor, lymphotoxins, transforming growth factors). These cytokines bind to specific cellular receptors, resulting in changes in the form and function of the target bone cells and variable activation of genes coding for extracellular matrix proteins and proteinases which are responsible for remodelling the matrix. The synthesis and release of eicosanoids such as prostaglandins (e.g. PGE2) are frequent associated events. PGE2, in turn, affects several functions of the skeletal tissue cells as well as the lymphocytes and monocytes in their environment. The mesenchymal cells may also be induced to release ligands such as colony-stimulating factors, other cellular products or hormones resulting in a system of feedback and amplification loops. The cellular responses are thus subject to multiple controls not only determined by these ligands acting on their respective receptors but also by the pathways of signal transduction and how they, in turn, are influenced by interactions with molecules within the cells.
