Molecular analysis of Leukemia Inhibitory Factor, LIF, signal transduction specific to the bone

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In order to elucidate the craniofacial bone characteristics, clinically experienced congenital hemifacial hypertrophic patient-derived cultured osteoblast-like cells were tested the cell proliferation activity under media condition with fetal calf serum, serum free, and cytokine (basic fibroblast growth factor, bFGF). Cell proliferation was dose-dependent on the fetal calf serum concentration, and bFGF in serum free media. The neutralizing antibody to bFGF significantly decreased the cell proliferation and DNA synthesis, suggesting that congenital hemifacial hypertrophic patient-derived osteoblast is regulated by exogenous cytokine treatment. This provoked the concept of the regulation of the craniofacial bone by the local cytokines. In comparative study of inferior alveolar nerve disturbance after mandibular sagittal split osteotomy by means of bicortical versus monocortical fixation, we found that there are no significant difference on bone fixation in both methods, however, the nerv … More e disturbance was significantly less frequent in monocortical fixation. This may explain there is no need of rigid fixation because the bone remodeling in situ accelerate and enhance the bone healing. Local factors such as cytokines and growth factors may be involved in the local bone formation. In the analysis of relapse after Le Fort I osteotomy in patients with cleft lip and palate, we elucidated the direction of the maxillary movement, amount, operative procedure and type of the cleft significantly affect the post-operative relapse and deviation during averaged two and half years period. This is another evidence of the local factors affiliating the bone remodeling and subsequent stability. Based on these clinical verifications, we designed the rat cranial bone defect model and tested the local cytokine gene therapy. Leukemia Inhibitory Factor, LIF, is not only well-known bone enhancing factor but its signal transduction is fully investigated. Therefore, we sought to clarify the local LIF gene in a expression vector would enhance the bone formation in cranial bone defect. LIF increased the bone mineral density shown by DEXA methods by three weeks post-operatively. In histology, there are more osteocytes in LIF-gene treated tissues than the control vehicle. LIF messages indicated by Immunohistochemistry and in situ hybridyzation were markedly increased in LIF-treated tissues. These data suggest local LIF is signally transduced and expressed to enhance the bone formation. Further study related to transcriptional factors and transcription-regulating factors associated with LIF expression are suggested in the future. Less