The Role of Cytokines in Bone Remodeling

Autocrine (skeletal to skeletal) or paracrine interactions (hematopoietic to skeletal) can be mediated by direct cell-to-cell contact, contact with matrix proteins, or binding of cytokines or growth factors to their cognate receptors. Cytokines appear to play an important role in the regulation of bone resorption and formation during pathologic bone remodeling and may also play a central role during normal remodeling. The ability of osteoblasts to respond to a specific set of cytokines is restricted by the expression of cell surface receptors. Binding of cytokine (ligand) to its receptor generates a signaling event from the plasma membrane to the nucleus, resulting in increases in the transcription of specific genes and, ultimately, the activation of different cellular processes. One such process is the secretion of a specific set of cytokines; the specific cytokine(s) secreted is dependent on the activation signal and is necessarily limited to the repertoire of cytokines that osteoblasts are capable of secreting. The secretion and binding of cytokines and growth factors forms the autocrine and paracrine circuitry involved in the regulation of bone remodeling.