Stimulation of Fos- and Jun-related Genes During Distraction Osteogenesis

Department of Anatomy and Cell Biology, The Bruce Rappaport Faculty of Medicine, Technion, Israel.
Journal of Histochemistry and Cytochemistry (Impact Factor: 1.96). 10/2003; 51(9):1161-8. DOI: 10.1177/002215540305100906
Source: PubMed


Bone cells respond to mechanical stimulation by gene expression. The molecular events involved in the translation of mechanical stimulation into cell proliferation and bone formation are not yet well understood. We looked for the expression of early-response genes of the AP-1 transcription factor complex in an in vivo bone regeneration system subjected to mechanical forces because these genes were found to be related to mechanotransduction and important for bone development. Sheep maxillary bone was distracted daily for 15 days. c-Jun and c-Fos were evaluated by Northern blotting analysis and immunohistochemistry in biopsy specimens removed at 8 and 15 days and were compared with post-osteotomy but not distracted repair tissue. Elevated levels of c-Jun and c-Fos mRNA were found after 8 days of distraction. Likewise, mesenchyme-like and fibroblast-like cells composing the 8-day distracted regeneration tissue showed increases in the intensity of immunostaining compared to cells in the corresponding non-distracted fracture repair tissue. After 15 days of distraction, when bone trabeculae start to form distally and proximally in the distracted regeneration tissue, mostly preosteoblasts and osteoblasts retained c-Fos and c-Jun immunoreactivity, similar to bone-associated cells in control non-distracted fracture repair tissue. We propose that the elevated expression of c-Jun and c-Fos is related to mechanical stimulation in this in vivo bone regeneration system.

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Available from: Adi Rachmiel, Oct 16, 2014
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    • "Associated with breast cancer [44] Unknown. JUN The c-Jun NH2-terminal Kinase Promotes Insulin Resistance [45] Proto-oncogene, in the KEGG pathway of colorectal cancer [38] Associated with osteogenesis [46] [47] NRIP1* Down-regulated in obese subjects, may suggest a compensatory mechanism to favor energy expenditure and reduce fat accumulation in obesity states [48] Unknown. Involved in regulation of E2F1, an oncogene [49] Modulates transcriptional activity of the estrogen receptor. "
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    ABSTRACT: Epidemiological studies suggested that obesity increases the risk of colorectal cancer (CRC). The genetic connection between CRC and obesity is multifactorial and inconclusive. In this study, we hypothesize that the study of shared comorbid diseases between CRC and obesity can offer unique insights into common genetic basis of these two diseases. We constructed a comorbidity network based on mining health data for millions of patients. We developed a novel approach and extracted the diseases that play critical roles in connecting obesity and CRC in the comorbidity network. Our approach was able to prioritize metabolic syndrome and diabetes, which are known to be associated with obesity and CRC through insulin resistance pathways. Interestingly, we found that osteoporosis was highly associated with the connection between obesity and CRC. Through gene expression meta-analysis, we identified novel genes shared among CRC, obesity and osteoporosis. Literature evidences support that these genes may contribute in explaining the genetic overlaps between obesity and CRC.
    AMIA summit 2015; 03/2015
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    • "It is generally suggested that distraction forces leading to cellular deformation are signalled to the cellular genome through mechanotransduction. Nuclear proto-oncogene c-fos and c-jun are found to be unregulated at early stages of distraction and are related to the mechanotransduction and embryonic bone development.[9] "
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    ABSTRACT: Limb lengthening by distraction osteogenesis was first described in 1905. The technique did not gain wide acceptance until Gavril Ilizarov identified the physiologic and mechanical factors governing successful regeneration of bone formation. Distraction osteogenesis is a new variation of more traditional orthognathic surgical procedure for the correction of dentofacial deformities. It is most commonly used for the correction of more severe deformities and syndromes of both the maxilla and the mandible and can also be used in children at ages previously untreatable. The basic technique includes surgical fracture of deformed bone, insertion of device, 5-7 days rest, and gradual separation of bony segments by subsequent activation at the rate of 1 mm per day, followed by an 8-12 weeks consolidation phase. This allows surgeons, the lengthening and reshaping of deformed bone. The aim of this paper is to review the principle, technical considerations, applications and limitations of distraction osteogenesis. The application of osteodistraction offers novel solutions for surgical-orthodontic management of developmental anomalies of the craniofacial skeleton as bone may be molded into different shapes along with the soft tissue component gradually thereby resulting in less relapse.
    Dental research journal 03/2014; 11(1):16-26.
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    • "Bone cells respond to mechanical stimulation by gene expression. Lewinson et al20 have demonstrated that mechanical stimulation of regenerating bone by daily distraction stimulates the expression of early-response genes of the activator protein 1 family of transcription factors. After 15 days of distraction, when bone trabeculae start to form, mostly preosteoblasts and osteoblasts retained c-Fos and c-Jun immunoreactivity. "
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    ABSTRACT: Gradual bone lengthening using distraction osteogenesis principles is the gold standard for the treatment of hypoplastic facial bones. However, the long treatment time is a major disadvantage of the lengthening procedures. The aim of this study is to review the current literature and summarize the cellular and molecular events occurring during membranous craniofacial distraction osteogenesis. Mechanical stimulation by distraction induces biological responses of skeletal regeneration that is accomplished by a cascade of biological processes that may include differentiation of pluripotential tissue, angiogenesis, osteogenesis, mineralization, and remodeling. There are complex interactions between bone-forming osteoblasts and other cells present within the bone microenvironment, particularly vascular endothelial cells that may be pivotal members of a complex interactive communication network in bone. Studies have implicated number of cytokines that are intimately involved in the regulation of bone synthesis and turnover. The gene regulation of numerous cytokines (transforming growth factor-β, bone morphogenetic proteins, insulin-like growth factor-1, and fibroblast growth factor-2) and extracellular matrix proteins (osteonectin, osteopontin) during distraction osteogenesis has been best characterized and discussed. Understanding the biomolecular mechanisms that mediate membranous distraction osteogenesis may guide the development of targeted strategies designed to improve distraction osteogenesis and accelerate bone regeneration that may lead to shorten the treatment duration.
    01/2014; 2(1):e98. DOI:10.1097/GOX.0000000000000043
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