The Role of Cytokines and Growth Factors as Mediators of the Effects of Systemic Hormones at the Bone Local Level

Abstract

Bone tissue is being continuously remodeled by the integrated activity of bone-resorbing osteoclasts and bone-forming osteoblasts. Because bone remodeling takes place in discrete foci throughout the skeleton, local mechanisms must play a critical role in its regulation. Several cytokines and other locally released factors exert marked effects on bone cells. Many experimental studies show that calciotropic hormones modulate cytokine expression. Indeed, a number of studies suggest that cytokines are actually involved in the mechanisms that mediate the effects of calciotropic hormones at the areas of bone being remodeled. However, the results are often conflicting. Moreover, most published studies have been carried out by testing the effects of pharmacological concentrations of hormones on cytokine production by bone cells. This type of study often gives little information on the physiological role of the factors tested. Thus, although evidence for a role of cytokines as mediators of hormone effects at the bone local level is rapidly accumulating, more data are needed in order to better understand the actual role of those factors in bone physiology and pathophysiology. In vivo studies and particularly those analyzing the consequences of the lack of activity of a particular cytokine or hormone are likely to be particularly informative.