Cytokines and skeletal physiology.
Cytokines are soluble factors that play a critical role in mediating cell to cell interactions within skeletal tissues. These effects are mediated by paracrine, autocrine, and juxtacrine mechanisms. There are also examples in which the cytokines can function in an endocrine fashion. The regulatory functions of the cytokines are performed throughout life, beginning with bone growth and development and continuing in the mature organism, in which bone remodeling is regulated. The cytokines can be grouped into distinct families based on their principal biologic activity and cell target. However, the activities of the cytokines are pleiotropic, and they exhibit considerable overlap and redundancy in their actions. The molecular cloning of the cytokines and their receptors and elucidation of their common structural features have aided in the understanding of the molecular basis for the redundancy and pleiotropy of cytokine effects. Examination of most physiologic processes in which cytokines play an important regulatory role reveals that cytokines rarely exert their biologic activities in isolation. Instead, these soluble factors usually are produced locally in concert with many other cytokines. The interaction of these structurally and functionally distinct factors in a highly ordered temporal and spatial sequence creates a cytokine network that ultimately determines a given tissue's response. Continued investigation into the molecular and biologic mechanisms by which cytokines regulate bone cell function will provide additional insights into normal bone physiology and permit more effective and specific use of these factors in the treatment of skeletal disorders.