Monocyte chemoattractant protein-1 induces monocyte recruitment that is associated with an increase in numbers of osteoblasts

Monocyte chemoattractant protein-1 (MCP-1) is a member of the chemokine family of cytokines. The principal function of MCP-1 is thought to be the stimulation of monocyte recruitment. Monocyte products are potential regulators of bone cell activity. Growth factors produced by monocytes may stimulate bone formation, while cytokines such as IL-1 and IL-6 can induce bone resorption. To determine whether MCP-1 enhances recruitment of monocytes during bone healing, studies were carried out in which MCP-1 was applied to osseous sites in vivo. Changes in monocyte number were determined by immunohistochemistry using the antibody ED-1 specific for peripheral monocytic cells. The effect of MCP-1 on osteoblast number was determined by counting the number of alkaline phosphatase positive cells in close proximity to bone. For comparison, osteoblast number was also determined following stimulation with platelet-derived growth factor (PDGF)-BB plus IGF-1 in vivo. Results indicate that MCP-1 stimulated a large increase in monocyte recruitment compared to vehicle alone. An increase in monocytes induced by MCP-1 was associated with an increase in the number of osteoblasts lining the bone surface, although not to the same magnitude as a positive control, PDGF-BB, and IGF-1. These results indicate that MCP-1 induces the recruitment of monocytes to bone and suggest that the recruitment is associated with an increase in osteoblast number. This is likely to occur via indirect mechanisms, because MCP-1 did not directly enhance DNA synthesis in osteoblastic cells in vitro. Thus, activated mononuclear phagocytes may play an important role in osseous wound healing by stimulating proliferation of osteoblastic cells, presumably through the elaboration of growth factors.