Identification of macrophage migration inhibitory factor in murine neonatal calvariae and osteoblasts

Abstract

SUMMARYBone resorption and formation are dynamic processes that occur in both normal and injured bone tissues. Regulation of these processes is mediated at the local level by cytokines and growth factors. Macrophage migration inhibitory factor (MIF) is one of the proinflammatory cytokines that activates macrophages and regulates production of other cytokines, such as tumour necrosis factor-a and interleukin-1. We here demonstrate, by reverse transcription-polymerase chain reaction, high expression of MIF mRNA in murine osteoblasts obtained from mouse neonatal calvariae and murine osteoblastic MC3T3-E1 cells. The presence of MIF protein in the osteoblasts was confirmed by Western blot analysis using anti-rat MIF antibody. Moreover, the immunohistochemical study revealed that MIF was localized largely in the cytoplasm. The pathophysiological function of MIF remains undefined; however, the present results suggest that MIF takes part in the osseous metabolism as well as in immunological events.

Macrophage Migration Inhibitory Factor Up-regulates Matrix Metalloproteinase-9 and -13 in Rat Osteoblasts

“…We found significant up-regulation of MMP-9 mRNA, and a slight increase of MMP-2 mRNA, consistent with a previous finding (43). Considering these facts, including our previous report revealing high expression of MIF in murine osteoblasts (17), it is likely that MIF may act on osteoblasts as an autocrine factor promoting bone resorption rather than bone formation. Indeed, MIF-overexpressing transgenic mouse (16-week-old) shows signs of osteoporosis.…”

“…In a previous study, we demonstrated that mouse osteoblasts expressed high amounts of MIF (17); however, its pathophysiological role in the bone tissues remains to be elucidated. We herein report for the first time that MIF enhances the MMP-13 mRNA level in osteoblasts obtained from newborn rat calvariae.…”

Increased expression of macrophage migration inhibitory factor during fracture healing in rats

“…The involvement of MIF in cell differentiation and proliferation has been reported. MIF is present in highly proliferative tissues such as the corneal epithelium, basal cell layers of the skin epidermis, neonatal rat calvaria, and the early embryonal chicken lens (Wistow et al 1993;Matsuda et al 1996;Onodera et al 1996;Shimizu et al 1996). MIF also promotes proliferation of fibroblasts (Mitchell et al 1999;Lacey et al 2003).…”

Effect of Macrophage Migration Inhibition Factor on the Content of Stromal Precursor Cells in Mouse Bone Marrow and Efficiency of Bone Marrow Precursor Cell Cloning In Vitro

“…It was found that MIF elevated the content of MMP-13 (collagenase 3) mRNA in rat osteoblasts [10]. High level of MIF mRNA expression in MC3T3-E1 mouse osteoblasts was noted [11].…”